2024/12/21 更新

お知らせ

 

写真a

メノ チカラ
目野 主税
MENO CHIKARA
所属
医学研究院 基礎医学部門 教授
医学部 医学科(併任)
医学系学府 医学専攻(併任)
医学系学府 医療経営・管理学専攻(併任)
職名
教授
プロフィール
研究活動:  私たちの体は外観は左右対称ですが、臓器は顕著な左右非対称性を示します。このような左右非対称性はどのようにして形成されるのでしょうか?私たちはマウス胚の左側で発現する分泌因子Lefty1, Lefty2を見出し、この遺伝子を糸口に左右軸形成の全体像を明らかにしてきました。Leftyは同じく胚の左側で発現する分泌因子Nodalを抑制し、Nodal-Leftyの相互関係が左右を決定する上で重要な役割を果たします。さらに、この相互関係は左右形成のみならず、前後の形成においても必須の役割を果たしています。現在、体軸形成の諸問題に取り組みながら、様々な発生現象に興味を持って研究を進めています。 教育活動:  医学部、医学系学府の「発生学」関連の授業を担当・分担しています。
外部リンク

学位

  • 博士(医学) ( 大阪大学 )

経歴

  • 大阪大学   

研究テーマ・研究キーワード

  • 研究テーマ: マウス胚発生における体軸形成の分子機構の解析

    研究キーワード: 左右軸、前後軸、胚発生

    研究期間: 1995年4月 - 現在

  • 研究テーマ: 心臓発生における左右軸の役割の解析

    研究キーワード: 心臓発生、左右軸

    研究期間: - 現在

  • 研究テーマ: 哺乳類初期発生のメカニズムの解析

    研究キーワード: 初期発生

    研究期間: - 現在

  • 研究テーマ: 先天性心疾患発症メカニズムの解析

    研究キーワード: 先天性心疾患

    研究期間: - 現在

受賞

  • 文部科学大臣表彰若手科学者賞

    2009年4月  

論文

  • Hyperglycaemia induces diet-dependent defects of the left-right axis by lowering intracellular pH 国際誌

    Matsuoka, R; Kitajima, K; Nii, T; Zou, ZA; Tanaka, K; Joo, K; Ohkawa, Y; Ohga, S; Meno, C

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   1871 ( 1 )   167550 - 167550   2025年1月   ISSN:0925-4439 eISSN:1879-260X

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Biochimica et Biophysica Acta - Molecular Basis of Disease  

    Pregestational diabetes is a risk factor for congenital anomalies, including heterotaxy syndrome, a rare birth defect characterized by the abnormal arrangement of organs relative to the left-right (L-R) body axis. To provide insight into the underlying mechanism by which diabetes induces heterotaxy, we here analyzed the L-R axis of mouse embryos of diabetic dams. Various Pitx2 expression patterns indicative of disruption of L-R axis formation were apparent in such embryos. Expression of Nodal at the node, which triggers a Nodal-Pitx2 expression cascade in lateral plate mesoderm, showed marked regression associated with L-R axis malformation. This regression was similar to that apparent in Wnt3a−/− embryos, and canonical Wnt signalling was indeed found to be downregulated in embryos of diabetic dams. RNA sequencing revealed dysregulation of glycolysis in embryos of diabetic dams, and high glucose lowered intracellular pH in the primitive streak, leading to the suppression of Wnt signalling and the regression of Nodal expression. Of note, maternal vitamin A intake increased the incidence of L-R axis defects in embryos of diabetic dams, with dysregulation of retinoic acid metabolism being apparent in these embryos and in Wnt3a−/− embryos. Our results shed light on the mechanisms underlying embryopathies associated with maternal diabetes and suggest the importance of diet for prevention of heterotaxy.

    DOI: 10.1016/j.bbadis.2024.167550

    Web of Science

    Scopus

    PubMed

    researchmap

  • descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques 国際誌

    Otomo, K; Omura, T; Nozawa, Y; Edwards, SJ; Sato, Y; Saito, Y; Yagishita, S; Uchida, H; Watakabe, Y; Naitou, K; Yanai, R; Sahara, N; Takagi, S; Katayama, R; Iwata, Y; Shiokawa, T; Hayakawa, Y; Otsuka, K; Watanabe-Takano, H; Haneda, Y; Fukuhara, S; Fujiwara, M; Nii, T; Meno, C; Takeshita, N; Yashiro, K; Rocabado, JMR; Kaku, M; Yamada, T; Oishi, Y; Koike, H; Cheng, YL; Sekine, K; Koga, J; Sugiyama, K; Kimura, K; Karube, F; Kim, H; Manabe, I; Nemoto, T; Tainaka, K; Hamada, A; Brismar, H; Susaki, EA

    NATURE COMMUNICATIONS   15 ( 1 )   4941 - 4941   2024年6月   eISSN:2041-1723

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Communications  

    Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000–50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced (https://github.com/dbsb-juntendo/descSPIM), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies.

    DOI: 10.1038/s41467-024-49131-1

    Web of Science

    Scopus

    PubMed

    researchmap

  • High-depth spatial transcriptome analysis by photo-isolation chemistry. 国際誌

    Mizuki Honda, Shinya Oki, Ryuichi Kimura, Akihito Harada, Kazumitsu Maehara, Kaori Tanaka, Chikara Meno, Yasuyuki Ohkawa

    Nature communications   12 ( 1 )   4416 - 4416   2021年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In multicellular organisms, expression profiling in spatially defined regions is crucial to elucidate cell interactions and functions. Here, we establish a transcriptome profiling method coupled with photo-isolation chemistry (PIC) that allows the determination of expression profiles specifically from photo-irradiated regions of interest. PIC uses photo-caged oligodeoxynucleotides for in situ reverse transcription. PIC transcriptome analysis detects genes specifically expressed in small distinct areas of the mouse embryo. Photo-irradiation of single cells demonstrated that approximately 8,000 genes were detected with 7 × 104 unique read counts. Furthermore, PIC transcriptome analysis is applicable to the subcellular and subnuclear microstructures (stress granules and nuclear speckles, respectively), where hundreds of genes can be detected as being specifically localised. The spatial density of the read counts is higher than 100 per square micrometre. Thus, PIC enables high-depth transcriptome profiles to be determined from limited regions up to subcellular and subnuclear resolutions.

    DOI: 10.1038/s41467-021-24691-8

  • Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation. 国際誌

    Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, Mitsuyoshi Nakao, Takehiko Yokomizo

    Cellular & molecular immunology   2020年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Leukotriene B4 (LTB4) receptor 1 (BLT1) is a chemotactic G protein-coupled receptor expressed by leukocytes, such as granulocytes, macrophages, and activated T cells. Although there is growing evidence that BLT1 plays crucial roles in immune responses, its role in dendritic cells remains largely unknown. Here, we identified novel DC subsets defined by the expression of BLT1, namely, BLT1hi and BLT1lo DCs. We also found that BLT1hi and BLT1lo DCs differentially migrated toward LTB4 and CCL21, a lymph node-homing chemoattractant, respectively. By generating LTB4-producing enzyme LTA4H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout (BLT1 cKO) mice, we showed that the migration of BLT1hi DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1lo DCs accelerated T cell proliferation by producing IL-2. Collectively, the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB4-BLT1 axis in the spatiotemporal regulation of distinct DC subsets.

    DOI: 10.1038/s41423-020-00559-7

  • Modeling early stages of endoderm development in epiblast stem cell aggregates with supply of extracellular matrices. 査読

    Sachiko Inamori, Mai Fujii, Sayaka Satake, Hideaki Iida, Machiko Teramoto, Tomoyuki Sumi, Chikara Meno, Yasuo Ishii, Hisato Kondoh

    Development, growth & differentiation   62 ( 4 )   243 - 259   2020年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Endoderm precursors expressing FoxA2 and Sox17 develop from the epiblast through the gastrulation process. In this study, we developed an experimental system to model the endoderm-generating gastrulation process using epiblast stem cells (EpiSCs). To this end, we established an EpiSC line i22, in which enhanced green fluorescent protein is coexpressed with Foxa2. Culturing i22 EpiSCs as aggregates for a few days was sufficient to initiate Foxa2 expression, and further culturing of the aggregates in Matrigel promoted the sequential activation of transcription factor genes involved in endoderm precursor development, e.g., Eomes, Gsc, and Sox17. In aggregation culture of i22 cells for 3 days, all cells expressed POU5F1, SOX2, and E-cadherin, a signature of the epiblast, whereas expression of GATA4 and SOX17 was also activated moderately in dispersed cells, suggesting priming of these cells to endodermal development. Embedding the aggregates in Matrigel for further 3 days elicited migration of the cells into the lumen of laminin-rich matrices covering the aggregates, in which FOXA2 and SOX17 were expressed at a high level with the concomitant loss of E-cadherin, indicating the migratory phase of endodermal precursors. Prolonged culturing of the aggregates generated three segregating cell populations found in post-gastrulation stage embryos: (1) definitive endoderm co-expressing high SOX17, GATA4, and E-cadherin, (2) mesodermal cells expressing a low level of GATA4 and lacking E-cadherin, and (3) primed epiblast cells expressing POU5F1, SOX2 without E-cadherin. Thus, aggregation of EpiSCs followed by embedding of aggregates in the laminin-rich matrix models the gastrulation-dependent endoderm precursor development.

    DOI: 10.1111/dgd.12663

  • Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice. 査読 国際誌

    Rie Saba, Keiko Kitajima, Lucille Rainbow, Silvia Engert, Mami Uemura, Hidekazu Ishida, Ioannis Kokkinopoulos, Yasunori Shintani, Shigeru Miyagawa, Yoshiakira Kanai, Masami Kanai-Azuma, Peter Koopman, Chikara Meno, John Kenny, Heiko Lickert, Yumiko Saga, Ken Suzuki, Yoshiki Sawa, Kenta Yashiro

    Scientific reports   9 ( 1 )   11953 - 11953   2019年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5+ cardiac progenitor cells (CPCs) that express the Sry-type HMG box gene Sox17 from embryonic day (E) 7.5 to E8.5 specifically differentiate into the endocardium in mouse embryos. Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non-cell-autonomous manner in the Sox17 mutant, likely as a consequence of down-regulation of NOTCH signaling. An unknown signal, regulated by Sox17 and required for nurturing of the myocardium, is responsible for the reduction in NOTCH-related genes in the mutant embryos. Our results thus provide insight into differentiation of the endocardium and its role in heart development.

    DOI: 10.1038/s41598-019-48321-y

  • ChIP-Atlas: a data-mining suite powered by full integration of public ChIP-seq data. 査読 国際誌

    Shinya Oki, Tazro Ohta, Go Shioi, Hideki Hatanaka, Osamu Ogasawara, Yoshihiro Okuda, Hideya Kawaji, Ryo Nakaki, Jun Sese, Chikara Meno

    EMBO reports   19 ( 12 )   2018年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have fully integrated public chromatin chromatin immunoprecipitation sequencing (ChIP-seq) and DNase-seq data (n > 70,000) derived from six representative model organisms (human, mouse, rat, fruit fly, nematode, and budding yeast), and have devised a data-mining platform-designated ChIP-Atlas (http://chip-atlas.org). ChIP-Atlas is able to show alignment and peak-call results for all public ChIP-seq and DNase-seq data archived in the NCBI Sequence Read Archive (SRA), which encompasses data derived from GEO, ArrayExpress, DDBJ, ENCODE, Roadmap Epigenomics, and the scientific literature. All peak-call data are integrated to visualize multiple histone modifications and binding sites of transcriptional regulators (TRs) at given genomic loci. The integrated data can be further analyzed to show TR-gene and TR-TR interactions, as well as to examine enrichment of protein binding for given multiple genomic coordinates or gene names. ChIP-Atlas is superior to other platforms in terms of data number and functionality for data mining across thousands of ChIP-seq experiments, and it provides insight into gene regulatory networks and epigenetic mechanisms.

    DOI: 10.15252/embr.201846255

  • Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters. 査読 国際誌

    Ryo Nabeshima, Osamu Nishimura, Takako Maeda, Natsumi Shimizu, Takahiro Ide, Kenta Yashiro, Yasuo Sakai, Chikara Meno, Mitsutaka Kadota, Hidetaka Shiratori, Shigehiro Kuraku, Hiroshi Hamada

    eLife   7   2018年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have examined the role of Fam60a, a gene highly expressed in embryonic stem cells, in mouse development. Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex, and most Fam60a-/- embryos manifest hypoplasia of visceral organs and die in utero. Fam60a is recruited to the promoter regions of a subset of genes, with the expression of these genes being either up- or down-regulated in Fam60a-/- embryos. The DNA methylation level of the Fam60a target gene Adhfe1 is maintained at embryonic day (E) 7.5 but markedly reduced at E9.5 in Fam60a-/- embryos, suggesting that DNA demethylation is enhanced in the mutant. Examination of genome-wide DNA methylation identified several differentially methylated regions, which were preferentially hypomethylated, in Fam60a-/- embryos. Our data suggest that Fam60a is required for proper embryogenesis, at least in part as a result of its regulation of DNA methylation at specific gene promoters.

    DOI: 10.7554/eLife.36435

  • Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells. 査読 国際誌

    Yuichiro Semba, Akihito Harada, Kazumitsu Maehara, Shinya Oki, Chikara Meno, Jun Ueda, Kazuo Yamagata, Atsushi Suzuki, Mitsuho Onimaru, Jumpei Nogami, Seiji Okada, Koichi Akashi, Yasuyuki Ohkawa

    Nucleic acids research   45 ( 15 )   8758 - 8772   2017年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.

    DOI: 10.1093/nar/gkx475

  • Chd5 Regulates MuERV-L/MERVL Expression in Mouse Embryonic Stem Cells Via H3K27me3 Modification and Histone H3.1/H3.2. 査読 国際誌

    Masayasu Hayashi, Kazumitsu Maehara, Akihito Harada, Yuichiro Semba, Kensuke Kudo, Hidehisa Takahashi, Shinya Oki, Chikara Meno, Kenji Ichiyanagi, Koichi Akashi, Yasuyuki Ohkawa

    Journal of cellular biochemistry   117 ( 3 )   780 - 92   2016年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chd5 is an essential factor for neuronal differentiation and spermatogenesis and is a known tumor suppressor. H3K27me3 and H3K4un are modifications recognized by Chd5; however, it remains unclear how Chd5 remodels chromatin structure. We completely disrupted the Chd5 locus using the CRISPR-Cas9 system to generate a 52 kbp long deletion and analyzed Chd5 function in mouse embryonic stem cells. Our findings show that Chd5 represses murine endogenous retrovirus-L (MuERV-L/MERVL), an endogenous retrovirus-derived retrotransposon, by regulating H3K27me3 and H3.1/H3.2 function.

    DOI: 10.1002/jcb.25368

  • Leukotriene B4 receptor type 2 (BLT2) enhances skin barrier function by regulating tight junction proteins. 査読 国際誌

    Yumiko Ishii, Kazuko Saeki, Min Liu, Fumiyuki Sasaki, Tomoaki Koga, Keiko Kitajima, Chikara Meno, Toshiaki Okuno, Takehiko Yokomizo

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   30 ( 2 )   933 - 47   2016年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    GPCRs are involved in numerous physiologic functions and are important drug targets. Although the epithelial barrier is important for protection from invading pathogens, the correlation between GPCRs and epithelial barrier function remains unknown. Leukotriene B4 (LTB4) receptor type 2 (BLT2), mainly expressed in epithelial cells, is a GPCR for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. In our study, BLT2 localized at the lateral membrane in BLT2-overexpressing Madin-Darby canine kidney (MDCK) II cells and in the small intestine of BLT2-transgenic mice. BLT2-deficient mice exhibited higher transepidermal water loss and were more sensitive to epicutaneous sensitization. MDCK-BLT2 cells recovered transepithelial electrical resistance (TER) after a calcium switch faster than did MDCK-Mock cells, and 12-HHT stimulation accelerated TER recovery only in MDCK-BLT2 cells. Quantitative PCR and immunoblot analyses revealed that the 12-HHT/BLT2 axis up-regulated claudin-4 (CLDN4) expression in MDCK-BLT2 cells and human primary keratinocytes, and CLDN4 knockdown abolished 12-HHT-dependent TER recovery. Acceleration of TER recovery and induction of CLDN4 expression by 12-HHT stimulation were abolished by inhibition of Gαi protein or p38 MAPK. These results show that 12-HHT/BLT2 enhances epithelial barrier function by increasing CLDN4 expression via the Gαi protein-p38 MAPK pathway.

    DOI: 10.1096/fj.15-279653

  • Hyperglycemia impairs left-right axis formation and thereby disturbs heart morphogenesis in mouse embryos. 査読 国際誌

    Masahiro Hachisuga, Shinya Oki, Keiko Kitajima, Satomi Ikuta, Tomoyuki Sumi, Kiyoko Kato, Norio Wake, Chikara Meno

    Proceedings of the National Academy of Sciences of the United States of America   112 ( 38 )   E5300-7   2015年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Congenital heart defects with heterotaxia are associated with pregestational diabetes mellitus. To provide insight into the mechanisms underlying such diabetes-related heart defects, we examined the effects of high-glucose concentrations on formation of the left-right axis in mouse embryos. Expression of Pitx2, which plays a key role in left-right asymmetric morphogenesis and cardiac development, was lost in the left lateral plate mesoderm of embryos of diabetic dams. Embryos exposed to high-glucose concentrations in culture also failed to express Nodal and Pitx2 in the left lateral plate mesoderm. The distribution of phosphorylated Smad2 revealed that Nodal activity in the node was attenuated, accounting for the failure of left-right axis formation. Consistent with this notion, Notch signal-dependent expression of Nodal-related genes in the node was also down-regulated in association with a reduced level of Notch signaling, suggesting that high-glucose concentrations impede Notch signaling and thereby hinder establishment of the left-right axis required for heart morphogenesis.

    DOI: 10.1073/pnas.1504529112

  • The importance of being isomeric 査読 国際誌

    Robert H. Anderson, Nigel A. Brown, Chikara Meno, Diane E. Spicer

    Clin Anat.   28 ( 4 )   477 - 486   2015年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: doi: 10.1002/ca.22517.

  • SraTailor: graphical user interface software for processing and visualizing ChIP-seq data. 査読 国際誌

    Shinya Oki, Kazumitsu Maehara, Yasuyuki Ohkawa, Chikara Meno

    Genes to cells : devoted to molecular & cellular mechanisms   19 ( 12 )   919 - 26   2014年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Raw data from ChIP-seq (chromatin immunoprecipitation combined with massively parallel DNA sequencing) experiments are deposited in public databases as SRAs (Sequence Read Archives) that are publically available to all researchers. However, to graphically visualize ChIP-seq data of interest, the corresponding SRAs must be downloaded and converted into BigWig format, a process that involves complicated command-line processing. This task requires users to possess skill with script languages and sequence data processing, a requirement that prevents a wide range of biologists from exploiting SRAs. To address these challenges, we developed SraTailor, a GUI (Graphical User Interface) software package that automatically converts an SRA into a BigWig-formatted file. Simplicity of use is one of the most notable features of SraTailor: entering an accession number of an SRA and clicking the mouse are the only steps required to obtain BigWig-formatted files and to graphically visualize the extents of reads at given loci. SraTailor is also able to make peak calls, generate files of other formats, process users' own data, and accept various command-line-like options. Therefore, this software makes ChIP-seq data fully exploitable by a wide range of biologists. SraTailor is freely available at http://www.devbio.med.kyushu-u.ac.jp/sra_tailor/, and runs on both Mac and Windows machines.

    DOI: 10.1111/gtc.12190

  • Wnt signaling regulates left-right axis formation in the node of mouse embryos. 査読 国際誌

    Keiko Kitajima, Shinya Oki, Yasuyuki Ohkawa, Tomoyuki Sumi, Chikara Meno

    Developmental biology   380 ( 2 )   222 - 32   2013年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The node triggers formation of the left-right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell-specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left-right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt-β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left-right difference in Nodal activity at the node for further amplification in lateral plate mesoderm.

    DOI: 10.1016/j.ydbio.2013.05.011

  • Epiblast ground state is controlled by canonical Wnt/β-catenin signaling in the postimplantation mouse embryo and epiblast stem cells. 査読 国際誌

    Tomoyuki Sumi, Shinya Oki, Keiko Kitajima, Chikara Meno

    PloS one   8 ( 5 )   e63378   2013年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Epiblast stem cells (EpiSCs) are primed pluripotent stem cells and can be derived from postimplantation mouse embryos. We now show that the absence of canonical Wnt/β-catenin signaling is essential for maintenance of the undifferentiated state in mouse EpiSCs and in the epiblast of mouse embryos. Attenuation of Wnt signaling with the small-molecule inhibitor XAV939 or deletion of the β-catenin gene blocked spontaneous differentiation of EpiSCs toward mesoderm and enhanced the expression of pluripotency factor genes, allowing propagation of EpiSCs as a homogeneous population. EpiSCs were efficiently established and propagated from single epiblast cells in the presence of both XAV939 and the Rho kinase (ROCK) inhibitor Y27632. Cell transplantation revealed that EpiSCs were able to contribute to primordial germ cells and descendants of all three germ layers in a host embryo, suggesting that they maintained pluripotency, even after prolonged culture with XAV939. Such an improvement in the homogeneity of pluripotency achieved with the use of a Wnt inhibitor should prove advantageous for manipulation of primed pluripotent stem cells.

    DOI: 10.1371/journal.pone.0063378

  • The dynamic right-to-left translocation of Cerl2 is involved in the regulation and termination of Nodal activity in the mouse node. 査読 国際誌

    José Manuel Inácio, Sara Marques, Tetsuya Nakamura, Kyosuke Shinohara, Chikara Meno, Hiroshi Hamada, José António Belo

    PloS one   8 ( 3 )   e60406   2013年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The determination of left-right body asymmetry in mouse embryos depends on the interplay of molecules in a highly sensitive structure, the node. Here, we show that the localization of Cerl2 protein does not correlate to its mRNA expression pattern, from 3-somite stage onwards. Instead, Cerl2 protein displays a nodal flow-dependent dynamic behavior that controls the activity of Nodal in the node, and the transmission of the laterality information to the left lateral plate mesoderm (LPM). Our results indicate that Cerl2 initially localizes and prevents the activation of Nodal genetic circuitry on the right side of the embryo, and later its right-to-left translocation shutdowns Nodal activity in the node. The consequent prolonged Nodal activity in the node by the absence of Cerl2 affects local Nodal expression and prolongs its expression in the LPM. Simultaneous genetic removal of both Nodal node inhibitors, Cerl2 and Lefty1, sustains even longer and bilateral this LPM expression.

    DOI: 10.1371/journal.pone.0060406

  • Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo. 査読 国際誌

    Teppei Noda, Shinya Oki, Keiko Kitajima, Tetsuro Harada, Shizuo Komune, Chikara Meno

    Developmental biology   362 ( 1 )   83 - 93   2012年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The mouse inner ear develops from a simple epithelial pouch, the otocyst, with the dorsal and ventral portions giving rise to the vestibule and cochlea, respectively. The otocyst undergoes a morphological change to generate flattened saclike structures, known as outpocketings, in the dorsal and lateral regions. The semicircular canals of the vestibule form from the periphery of the outpocketings, with the central region (the fusion plate) undergoing de-epithelialization and disappearing. However, little is known of the mechanism that orchestrates formation of the semicircular canals. We now show that the area of canonical Wnt signaling changes dynamically in the dorsal otocyst during its morphogenesis. The genes for several Wnt ligands were found to be expressed in the dorsal otocyst according to specific patterns, whereas those for secreted inhibitors of Wnt ligands were expressed exclusively in the ventral otocyst. With the use of whole-embryo culture in combination with potent modulators of canonical Wnt signaling, we found that forced persistence of such signaling resulted in impaired formation both of the lateral outpocketing and of the fusion plates of the dorsal outpocketing. Canonical Wnt signaling was found to suppress Netrin1 expression and to preserve the integrity of the outpocketing epithelium. In addition, inhibition of canonical Wnt signaling reduced the size of the otocyst, likely through suppression of cell proliferation and promotion of apoptosis. Our stage-specific functional analysis suggests that strict regulation of canonical Wnt signaling in the dorsal otocyst orchestrates the process of semicircular canal formation.

    DOI: 10.1016/j.ydbio.2011.11.019

  • DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. 査読 国際誌

    Fumiyuki Sanematsu, Masanori Hirashima, Mélanie Laurin, Ryosuke Takii, Akihiko Nishikimi, Keiko Kitajima, Guo Ding, Mamiko Noda, Yuzo Murata, Yoshihiko Tanaka, Sadahiko Masuko, Toshio Suda, Chikara Meno, Jean-François Côté, Takashi Nagasawa, Yoshinori Fukui

    Circulation research   107 ( 9 )   1102 - 5   2010年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    RATIONALE: During embryogenesis, the CXC chemokine ligand (CXCL)12 acts on endothelial cells to control cardiac development and angiogenesis. Although biological functions of CXCL12 are exerted in part through activation of the small GTPase Rac, the pathway leading from its receptor CXC chemokine receptor (CXCR)4 to Rac activation remains to be determined. OBJECTIVE: DOCK180 (dedicator of cytokinesis), an atypical Rac activator, has been implicated in various cellular functions. Here, we examined the role of DOCK180 in cardiovascular development. METHODS AND RESULTS: DOCK180 associates with ELMO (engulfment and cell motility) through the N-terminal region containing a Src homology 3 domain. We found that targeted deletion of the Src homology 3 domain of DOCK180 in mice leads to embryonic lethality with marked reduction of DOCK180 expression at the protein level. These mutant mice, as well as DOCK180-deficient mice, exhibited multiple cardiovascular abnormalities resembling those seen in CXCR4-deficient mice. In DOCK180 knocked down endothelial cells, CXCL12-induced Rac activation was impaired, resulting in a marked reduction of cell motility. CONCLUSIONS: These results suggest that DOCK180 links CXCR4 signaling to Rac activation to control endothelial cell migration during cardiovascular development.

    DOI: 10.1161/CIRCRESAHA.110.223388

  • Dissecting the role of Fgf signaling during gastrulation and left-right axis formation in mouse embryos using chemical inhibitors. 査読 国際誌

    Shinya Oki, Keiko Kitajima, Chikara Meno

    Developmental dynamics : an official publication of the American Association of Anatomists   239 ( 6 )   1768 - 78   2010年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Fgf signaling plays pivotal roles in mouse gastrulation and left-right axis formation. However, although genetic analyses have revealed important aspects of Fgf signaling in these processes, the temporal resolution of genetic studies is low. Here, we combined whole-embryo culture with application of chemical compounds to inhibit Fgf signaling at specific time points. We found that sodium chlorate and PD173074 are potent inhibitors of Fgf signaling in early mouse embryos. Fgf signaling is required for the epithelial-to-mesenchymal transition of the primitive streak before the onset of gastrulation. Once gastrulation begins, Fgf signaling specifies mesodermal fates via the Ras/MAPK downstream cascade. Finally, Fgf signaling on the posterior side of the embryo during gastrulation induces Nodal expression in the node via Tbx6-Dll1, the initial event required for Nodal expression in the left lateral plate mesoderm.

    DOI: 10.1002/dvdy.22282

  • Planar polarization of node cells determines the rotational axis of node cilia. 査読 国際誌

    Masakazu Hashimoto, Kyosuke Shinohara, Jianbo Wang, Shingo Ikeuchi, Satoko Yoshiba, Chikara Meno, Shigenori Nonaka, Shinji Takada, Kohei Hatta, Anthony Wynshaw-Boris, Hiroshi Hamada

    Nature cell biology   12 ( 2 )   170 - 6   2010年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Rotational movement of the node cilia generates a leftward fluid flow in the mouse embryo because the cilia are posteriorly tilted. However, it is not known how anterior-posterior information is translated into the posterior tilt of the node cilia. Here, we show that the basal body of node cilia is initially positioned centrally but then gradually shifts toward the posterior side of the node cells. Positioning of the basal body and unidirectional flow were found to be impaired in compound mutant mice lacking Dvl genes. Whereas the basal body was normally positioned in the node cells of Wnt3a(-/-) embryos, inhibition of Rac1, a component of the noncanonical Wnt signalling pathway, impaired the polarized localization of the basal body in wild-type embryos. Dvl2 and Dvl3 proteins were found to be localized to the apical side of the node cells, and their location was polarized to the posterior side of the cells before the posterior positioning of the basal body. These results suggest that posterior positioning of the basal body, which provides the posterior tilt to node cilia, is determined by planar polarization mediated by noncanonical Wnt signalling.

    DOI: 10.1038/ncb2020

  • Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos. 査読 国際誌

    Shinya Oki, Keiko Kitajima, Sara Marques, José António Belo, Takahiko Yokoyama, Hiroshi Hamada, Chikara Meno

    Development (Cambridge, England)   136 ( 23 )   3917 - 25   2009年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The node at the anterior tip of the primitive streak serves as an initial generator of the left-right (L-R) axis in mammalian embryos. We now show that a small disturbance in molecular signaling at the node is responsible for the L-R reversal of visceral organs in the inv mutant mouse. In the node of wild-type embryos, the expression of Nodal and Cerl2 (Dand5), which encodes an inhibitor of Nodal, is asymmetric, with the level of Nodal expression being higher on the left side and that of Cerl2 expression higher on the right. In inv/inv embryos, however, a localized reduction in the level of Cerl2 expression results in upregulation of the Nodal signal and a consequent induction of Lefty expression in the node. The ectopic expression of Lefty1 delays the onset of Nodal expression in the lateral plate mesoderm. L-R asymmetry of Cerl2 expression in the node also becomes reversed in a manner dependent on the Nodal signal. Nodal expression in the lateral plate mesoderm then appears on the right side, probably reflecting the balance between Nodal and Cerl2 in the node. The inhibition of Cerl2 expression by the Nodal signal suggests a mechanism for amplification of the cue for L-R asymmetry provided by nodal flow and for stabilization of asymmetric gene expression around the node. In inv/inv embryos, this system may function in reverse as a result of ectopic production of Lefty, which inhibits the Nodal signal on the left side in a manner dependent on leftward nodal flow.

    DOI: 10.1242/dev.039305

  • Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo. 査読 国際誌

    Masamichi Yamamoto, Hideyuki Beppu, Katsuyoshi Takaoka, Chikara Meno, En Li, Kohei Miyazono, Hiroshi Hamada

    The Journal of cell biology   184 ( 2 )   323 - 34   2009年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The anterior-posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.

    DOI: 10.1083/jcb.200808044

  • Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. 査読 国際誌

    Tetsuya Nakamura, Naoki Mine, Etsushi Nakaguchi, Atsushi Mochizuki, Masamichi Yamamoto, Kenta Yashiro, Chikara Meno, Hiroshi Hamada

    Developmental cell   11 ( 4 )   495 - 504   2006年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The bilateral symmetry of the mouse embryo is broken by leftward fluid flow in the node. However, it is unclear how this directional flow is then translated into the robust, left side-specific Nodal gene expression that determines and coordinates left-right situs throughout the embryo. While manipulating Nodal and Lefty gene expression, we have observed phenomena that are indicative of the involvement of a self-enhancement and lateral-inhibition (SELI) system. We constructed a mathematical SELI model that not only simulates, but also predicts, experimental data. As predicted by the model, Nodal expression initiates even on the right side. These results indicate that directional flow represents an initial small difference between the left and right sides of the embryo, but is insufficient to determine embryonic situs. Nodal and Lefty are deployed as a SELI system required to amplify this initial bias and convert it into robust asymmetry.

  • The mouse embryo autonomously acquires anterior-posterior polarity at implantation. 査読 国際誌

    Katsuyoshi Takaoka, Masamichi Yamamoto, Hidetaka Shiratori, Chikara Meno, Janet Rossant, Yukio Saijoh, Hiroshi Hamada

    Developmental cell   10 ( 4 )   451 - 9   2006年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The earliest recognizable sign of patterning of the mouse embryo along the anteroposterior (A-P) axis is the migration of the distal visceral endoderm (DVE) toward the future anterior side. Here we report an asymmetry in the mouse embryo at an unexpectedly early stage. The gene for Lefty1, a Nodal antagonist that influences the direction of DVE migration, was found to be asymmetrically expressed in the primitive endoderm of the implanting blastocyst. Lefty1 expression begins randomly in the inner cell mass (ICM) of the blastocyst but is regionalized to one side of the tilted ICM shortly after implantation. Asymmetric expression of Lefty1 can be established by in vitro culture, indicating that it does not require interaction with the uterus. The asymmetric Lefty1 expression is induced by Nodal signaling, although Nodal and genes for its effectors are expressed symmetrically. This asymmetry in molecular patterning of the mouse embryo pushes back the origin of the A-P body axis to the peri-implantation stage.

    DOI: 10.1016/j.devcel.2006.02.017

  • Basement membrane fragility underlies embryonic lethality in fukutin-null mice 査読

    Kurahashi H, Taniguchi M, Meno C, Taniguchi Y, Takeda S, Horie M, Otani H, Toda T

    Neurobiol Dis.   19 ( 1-2 )   208 - 217   2005年6月

     詳細を見る

    記述言語:その他  

  • Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. 査読 国際誌

    Masamichi Yamamoto, Yukio Saijoh, Aitana Perea-Gomez, William Shawlot, Richard R Behringer, Siew-Lan Ang, Hiroshi Hamada, Chikara Meno

    Nature   428 ( 6981 )   387 - 92   2004年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.

    DOI: 10.1038/nature02418

  • Nodal signaling induces the midline barrier by activating Nodal expression in the lateral plate. 査読 国際誌

    Masamichi Yamamoto, Naoki Mine, Kyoko Mochida, Yasuo Sakai, Yukio Saijoh, Chikara Meno, Hiroshi Hamada

    Development (Cambridge, England)   130 ( 9 )   1795 - 804   2003年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The transcription factor Foxh1 mediates Nodal signaling. The role of Foxh1 in left-right (LR) patterning was examined with mutant mice that lack this protein in lateral plate mesoderm (LPM). The mutant mice failed to express Nodal, Lefty2 and Pitx2 on the left side during embryogenesis and exhibited right isomerism. Ectopic introduction of Nodal into right LPM, by transplantation of left LPM or by electroporation of a Nodal vector, induced Nodal expression in wild-type embryos but not in the mutant. Ectopic Nodal expression in right LPM also induced Lefty1 expression in the floor plate. Nodal signaling thus initiates asymmetric Nodal expression in LPM and induces Lefty1 at the midline. Monitoring of Nodal activity in wild-type and Foxh1 mutant embryos suggested that Nodal activity travels from the node to left LPM, and from left LPM to the midline.

    DOI: 10.1242/dev.00408

  • Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. 査読 国際誌

    Aitana Perea-Gomez, Francis D J Vella, William Shawlot, Mustapha Oulad-Abdelghani, Claire Chazaud, Chikara Meno, Veronique Pfister, Lan Chen, Elizabeth Robertson, Hiroshi Hamada, Richard R Behringer, Siew-Lan Ang

    Developmental cell   3 ( 5 )   745 - 56   2002年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The anterior visceral endoderm plays a pivotal role in establishing anterior-posterior polarity of the mouse embryo, but the molecular nature of the signals required remains to be determined. Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo. This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene. Our findings provide support for a model whereby Cerberus-like and Lefty1 in the anterior visceral endoderm restrict primitive streak formation to the posterior end of mouse embryos by antagonizing Nodal signaling. Both antagonists are also required for proper patterning of the primitive streak.

  • Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion. 査読 国際誌

    Rui Sakuma, Yu-ichiro Ohnishi Yi, Chikara Meno, Hideta Fujii, Hou Juan, Jun Takeuchi, Toshihiko Ogura, En Li, Kohei Miyazono, Hiroshi Hamada

    Genes to cells : devoted to molecular & cellular mechanisms   7 ( 4 )   401 - 12   2002年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Two TGFbeta-related proteins, Nodal and Lefty, are implicated in early embryonic patterning of vertebrates. Genetic data suggest that Nodal is a signalling molecule, while Lefty is an antagonist of Nodal, but their precise function remains unknown. RESULTS: The signalling pathway of Nodal was investigated with the use of a Nodal-responsive assay system based on frog animal caps. Expression of dominant negative mutants of various receptors indicated that ALK4, and either ActRIIA or ActRIIB, function as type I and type II receptors for Nodal, respectively. A soluble form of Cripto lacking the COOH-terminal region interacted with Nodal but failed to mediate Nodal signalling, indicating that the native Cripto protein functions as a membrane-bound co-receptor for Nodal. Processed forms of Lefty proteins, both smaller and larger forms, inhibited Nodal signalling. Such Lefty-induced inhibition was rescued by excess ActRIIA or ActRIIB, suggesting that Lefty antagonizes Nodal signalling through competitive binding to the common receptor ActRIIA or ActRIIB. This idea was supported by the demonstration of a genetic interaction between lefty2 and ActRIIB in mouse. Behaviours of GFP-Nodal and GFP-Lefty2 proteins were also investigated in chick embryos. Both proteins could diffuse over a long distance, but the latter diffused faster than the former. CONCLUSIONS: Efficient inhibition of Nodal signals by Lefty may involve competitive binding of Lefty to the common receptors and faster diffusion of Lefty.

  • Establishment of vertebrate left-right asymmetry. 国際誌

    Hamada H, Meno C, Watanabe D, Saijoh Y.

    Nat Rev Genet.   2002年2月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

  • Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2 査読

    C Meno, J Takeuchi, R Sakuma, K Koshiba-Takeuchi, S Ohishi, Y Saijoh, J Miyazaki, P ten Dijke, T Ogura, H Hamada

    DEVELOPMENTAL CELL   1 ( 1 )   127 - 138   2001年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.

  • The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse 査読

    M Yamamoto, C Meno, Y Sakai, H Shiratori, K Mochida, Y Ikawa, Y Saijoh, H Hamada

    GENES & DEVELOPMENT   15 ( 10 )   1242 - 1256   2001年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    FoxH1 (FAST) is a transcription factor that mediates signaling by transforming growth factor-beta, Activin, and Nodal. The role of FoxH1 in development has now been investigated by the generation and analysis of FoxH1-deficient (FoxH1(-/-)) mice. The FoxH1(-/-) embryos showed various patterning defects that recapitulate most of the defects induced by the loss of Nodal signaling. A substantial proportion of FoxH1(-/-) embryos failed to orient the anterior-posterior (A-P) axis correctly, as do mice lacking Cripto, a coreceptor for Nodal. In less severely affected FoxH1(-/-) embryos, A-P polarity was established, but the primitive streak failed to elongate, resulting in the lack of a definitive node and its derivatives. Heterozygosity for nodal renders the FoxH1(-/-) phenotype more severe, indicative of a genetic interaction between FoxH1 and nodal. The expression of FoxH1 in the primitive endoderm rescued the A-P patterning defects, but not the midline defects, of FoxH1(-/-) mice. These results indicate that a Nodal-FoxH1 signaling pathway plays a central role in A-P patterning and node formation in the mouse.

  • The retinoic acid-inactivating enzyme CYP26 is essential for establishing an uneven distribution of retinoic acid along the anterio-posterior axis within the mouse embryo 査読

    Y Sakai, C Meno, H Fujii, J Nishino, H Shiratori, Y Saijoh, J Rossant, H Hamada

    GENES & DEVELOPMENT   15 ( 2 )   213 - 225   2001年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Retinoic acid (RA), a derivative of vitamin A, plays a pivotal role in vertebrate development. The level of RA may be determined by the balance between its synthesis and degradation. We have examined the role of CYP26, a P450 enzyme that may degrade RA, by generating mutant mice that lack CYP26. CYP26(-/-) mice exhibited anomalies, including caudal agenesis, similar to those induced by administration of excess RA. The concentration of endogenous RA, as revealed by marker gene activity, was markedly increased in the tailbud of the mutant animals, in which CYP26 is normally expressed. Expression of T (Brachyury) and Wnt3a in the tailbud was down-regulated in CYP26(-/-) mice, which may underlie the caudal truncation. The lack of CYP26 also resulted in homeotic transformation of vertebrae as well as in misspecification of the rostral hindbrain associated with anterior expansion of RA-positive domains. These results suggest that local degradation of RA by CYP26 is required for establishing an uneven distribution of RA along the anterio-posterior axis, which is essential for patterning the hindbrain, vertebrae, and tailbud.

    DOI: 10.1101/gad.851501

  • Mouse lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation 査読

    C Meno, K Gritsman, S Ohishi, Y Ohfuji, E Heckscher, K Mochida, A Shimono, H Kondoh, WS Talbot, EJ Robertson, AF Schier, H Hamada

    MOLECULAR CELL   4 ( 3 )   287 - 298   1999年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mammalian lefty and zebrafish antivin form a subgroup of the TGF beta superfamily. We report that mouse mutants for lefty2 have an expanded primitive! streak and form excess mesoderm, a phenotype opposite to that of mutants for the TGF beta gene nodal. Analogously, overexpression of Antivin or Lefty2 in zebrafish embryos blocks head and trunk mesoderm formation, a phenotype identical to that of mutants caused by loss of Nodal signaling. The lefty2 mutant phenotype is partially suppressed by heterozygosity for nodal. Similarly, the effects of Antivin and Lefty2 can be suppressed by overexpression of the nodal-related genes cyclops and squint or the extracellular domain of ActRIIB. Expression of antivin is dependent on Nodal signaling, revealing a feedback loop wherein Nodal signals induce their antagonists Lefty2 and Antivin to restrict Nodal signaling during gastrulation.

    DOI: 10.1016/S1097-2765(00)80331-7

  • GFR alpha 3, a component of the artemin receptor, is required for migration and survival of the superior cervical ganglion 査読

    J Nishino, K Mochida, Y Ohfuji, T Shimazaki, C Meno, S Ohishi, Y Matsuda, H Fujii, Y Saijoh, H Hamada

    NEURON   23 ( 4 )   725 - 736   1999年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    GFR alpha 3 is a component of the receptor for the neurotrophic factor artemin. The role of GFR alpha 3 in nervous system development was examined by generating mice in which the Gfr alpha 3 gene was disrupted. The Gfr alpha 3(-/-) mice exhibited severe defects in the superior cervical ganglion (SCG), whereas other ganglia appeared normal. SCG precursor cells in the mutant embryos failed to migrate to the correct position, and they subsequently failed to innervate the target organs. In wildtype embryos, Gfr alpha 3 was expressed in migrating SCG precursors, and artemin was expressed in and near the SCG. After birth, SCG neurons in the mutant mice underwent progressive cell death. These observations suggest that GFR alpha 3-mediated signaling is required both for the rostral migration of SCG precursors and for the survival of mature SCG neurons.

    DOI: 10.1016/S0896-6273(01)80031-3

  • Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry 査読

    H Yoshioka, C Meno, K Koshiba, M Sugihara, H Itoh, Y Ishimaru, T Inoue, H Ohuchi, EV Semina, JC Murray, H Hamada, S Noji

    CELL   94 ( 3 )   299 - 305   1998年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Signaling molecules such as Activin, Sonic hedgehog, Nodal, Lefty, and Vg1 have been found to be involved in determination of left-right (L-R) asymmetry in the chick, mouse, or frog. However, a common signaling pathway has not yet been identified in vertebrates. We report that Pitx2, a bicoid-type homeobox gene expressed asymmetrically in the left lateral plate mesoderm, may be involved in determination of L-R asymmetry in both mouse and chick. Since Pitx2 appears to be downstream of lefty-1 in the mouse pathway, we examined whether mouse Lefty proteins could affect the expression of Pitx2 in the chick. Our results indicate that a common pathway from lefty-1 to Pitx2 likely exists for determination of L-R asymmetry in vertebrates.

    DOI: 10.1016/S0092-8674(00)81473-7

  • lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal 査読

    C Meno, A Shimono, Y Saijoh, K Yashiro, K Mochida, S Ohishi, S Noji, H Kondoh, H Hamada

    CELL   94 ( 3 )   287 - 297   1998年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    lefty-1, leffy-2 and nodal are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) determination. The role of lefty-1 was examined by analyzing mutant mice lacking this gene. The lefty-1-deficient mice showed a variety of L-R positional defects in visceral organs. Unexpectedly, however, the most common feature of lefty-1(-/-) mice was thoracic left isomerism (rather than right isomerism). The lack of lefty-1 resulted in bilateral expression of nodal, lefty-2, and Pitx2 (a homeobox gene normally expressed on the left side). These observations suggest that the role of lefty-1 is to restrict the expression of lefty-2 and nodal to the left side, and that lefty-2 or nodal encodes a signal for "leftness."

    DOI: 10.1016/S0092-8674(00)81472-5

  • Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos 査読

    C Meno, Y Ito, Y Saijoh, Y Matsuda, K Tashiro, S Kuhara, H Hamada

    GENES TO CELLS   2 ( 8 )   513 - 524   1997年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Vertebrates have numerous lateral asymmetries in the position of their organs, but the molecular basis for the determination of left-right (L-R) asymmetries remains largely unknown. TGF beta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in GR determination.
    Results: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome. These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos. However, the major expression domains of the two genes are different: lefty-1 expression is predominantly confied to the left side of ventral neural tube, whereas lefty-2 is strongly expressed in the lateral plate mesoderm on the left side. In embryos homozygous for the iv and inv mutation, which cause situs inversus, the expression sites of both genes are affected, either reversed or bilaterally, indicating that lefty-1 and lefty-2 are downstream of iv and inv. Although Lefty-1 and Lefty-2 prepro-proteins are not readily processed in cultured cells, BMP2-Lefty chimeric proteins can be processed to a secreted form. We have examined the activities of Lefty-1 and Lefty-2 in Xenopus embryos. In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction. The direct neuralizing activities of Lefty-1 and Lefty-2 thus seem remarkably similar to those of BMP antagonists such as noggin and chordin, suggesting that the action of Lefty-1 and Lefty-2 may be to locally antagonize BMP (bone morphogenic protein)mediated signals in tissues positioned on the left side of the mouse embryos.
    Conclusion: There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a LR asymmetric fashion and are downstream of iv and inv. Lefty-1 and Lefty-2 possess direct neuralizing activity in Xenopus embryos, resembling the activities of BMP antagonists.

    DOI: 10.1046/j.1365-2443.1997.1400338.x

  • Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos 査読

    C Meno, Y Saijoh, H Fujii, M Ikeda, T Yokoyama, M Yokoyama, Y Toyoda, H Hamada

    NATURE   381 ( 6578 )   151 - 155   1996年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    EXAMPLES Of lateral asymmetry are often found in vertebrates, such as the heart being on the left side, but the molecular mechanism governing the establishment of this left-right (LR) handedness is unknown(1). A diffusible morphogen may determine L-R polarity(2), but a likely molecule has not so far been identified. Here we report on the gene lefty, a member of the transforming growth factor-beta family, which may encode a morphogen for L-R determination. Lefty protein contains the cysteine-knot motif(3) characteristic of this superfamily(4,5) and is secreted as a processed form of relative molecular mass 25K-32K. Surprisingly, lefty is expressed in the left half of gastrulating mouse embryos. This asymmetric expression is very transient and occurs just before the first sign of lateral asymmetry appears. In the mouse mutants iv and inv, which cause situs inversus, the sites of lefty expression are inverted, indicating that lefty is downstream of iv and inv. These results suggest that lefty may be involved in setting up L-R asymmetry in the organ systems of mammals.

    DOI: 10.1038/381151a0

  • Identification of putative downstream genes of Oct-3, a pluripotent cell-specific transcription factor 査読

    Y Saijoh, H Fujii, C Meno, M Sato, Y Hirota, S Nagamatsu, M Ikeda, H Hamada

    GENES TO CELLS   1 ( 2 )   239 - 252   1996年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Oct-3, a pluripotent cell-specific POU transcription factor, appears to be a key regulator in pluripotential early embryonic cells and germ cells. In order to study how pluripotency is maintained, it is essential to know what genes are regulated by Oct-3.
    Results: By employing a subtraction method, we identified several pluripotent cell-specific genes. Based upon expression patterns in various cell lines lacking or possessing Oct-3 function, about half of the genes were placed downstream of Oct-3. These downstream genes included a previously-known gene (Glut-3: a gene for a glucose transporter) and novel genes (226, 383 and 880). Their expression patterns paralleled that of Oct-3: all of these genes were highly expressed in pluripotent cells such as EC/ES cells, but switched off upon differentiation. More importantly, their expression was rescued in 'revertant' cells that ectopically acquired the Oct-3 transactivating function. Furthermore, the expression profiles of Glut-3, 226 and 383 during mouse development also overlapped that of Oct-3. The Glut-3 gene possessed multiple Oct-3 binding sites in its transcriptional regulatory regions, suggesting that at least one of the downstream genes was a direct target of Oct-3.
    Conclusions: A large proportion of pluripotent cell-specific genes appear to be downstream targets of Oct-3.

  • SYNCHRONOUS SPERM PENETRATION OF ZONA-FREE MOUSE EGGS IN-VITRO 査読

    Y TAKAHASHI, C MENO, E SATO, Y TOYODA

    BIOLOGY OF REPRODUCTION   53 ( 2 )   424 - 430   1995年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To synchronize sperm penetration of zona-free eggs immediately after insemination, zona-free eggs preloaded with Hoechst-33342 were inseminated under various conditions, Insemination was mostly conducted at 10 sperm/mu l. In preliminary experiments, fatty acid-free BSA (FAF) was more satisfactory for sperm penetration than fraction V BSA, and FAF was used in the following experiments. Only 26% of zona-free eggs were fertilized at 10 min after insemination when the eggs were inseminated immediately after zona removal and preloading. However, egg preincubation significantly improved the penetration rate (1 h preincubation: 63%, 2 h preincubation: 82% penetrated 10 min after insemination). Some eggs preincubated for 2 h were already penetrated at 3 min (7%), and the rate gradually increased in a time-dependent manner (3 min: 7%, 5 min: 30%, 10 min: 80%). The rate further improved as the sperm concentration was increased; the maximal level was obtained at 160 sperm/mu l. At 160 sperm/mu l, 54% of the eggs were penetrated at 3 min and 78% were at 5 min. These results indicate that it is possible to synchronize the sperm entry and that not only sperm but zona-free eggs should be preincubated before insemination. These data are considered valuable for investigating early events in fertilization.

▼全件表示

MISC

  • The importance of being isomeric. 査読

    Robert H Anderson, Nigel A Brown, Chikara Meno, Diane E Spicer

    Clinical anatomy (New York, N.Y.)   2015年5月

     詳細を見る

    記述言語:英語  

    In the normal individual, the parietal components of the body are mirror-imaged and appropriately described as isomeric. The thoraco-abdominal organs, in contrast, are lateralized. However, in "visceral heterotaxy," the thoraco-abdominal organs also show some degree of isomerism, best seen in the arrangement of the bronchial tree. Whether isomerism can be found within the heart remains controversial. One of two recent publications in this journal emphasized the crucial features of bronchial isomerism; the other, in contrast, confused the situation of isomerism within the heart. In this review, we show how the topic of cardiac isomerism is clarified by concentrating on the anatomical features of the cardiac components and determining how best they can be described. Appropriate manipulation of developing mice produces unequivocal evidence of isomerism of the atrial appendages, but with no evidence of ventricular isomerism. In hearts from patients with so-called "heterotaxy," only the atrial appendages, distinguished on the basis of the pectinate muscles lining their walls, are uniformly isomeric, permitting the syndrome to be differentiated into the subsets of left as opposed to right atrial appendage isomerism. Thus, controversies are defused by simply describing the isomerism of the atrial appendages rather than "atrial isomerism," recognizing the frequency of abnormal venoatrial connections in these settings. Any suggestion of ambiguity is removed by the equally simple expedient of describing all the variable cardiac features, describing the arrangements of the thoracic and abdominal organs separately should there be discordances.

    DOI: 10.1002/ca.22517

  • [Analysis of Wnt signaling during the morphogenesis of semicircular canal in mouse inner ear].

    Teppei Noda, Chikara Meno

    Fukuoka igaku zasshi = Hukuoka acta medica   2013年7月

     詳細を見る

    記述言語:日本語  

  • Establishment of vertebrate left-right asymmetry. 査読

    Hiroshi Hamada, Chikara Meno, Daisuke Watanabe, Yukio Saijoh

    Nature reviews. Genetics   2002年2月

     詳細を見る

    記述言語:英語  

    The generation of morphological, such as left-right, asymmetry during development is an integral part of the establishment of a body plan. Until recently, the molecular basis of left-right asymmetry was a mystery, but studies indicate that Nodal and the Lefty proteins, transforming growth factor-beta-related molecules, have a central role in generating asymmetric signals. Although the initial mechanism of symmetry breaking remains unknown, developmental biologists are beginning to analyse the pathway that leads to left-right asymmetry establishment and maintenance.

  • Role of asymmetric signals in left-right patterning in the mouse 査読

    H Hamada, C Meno, Y Saijoh, H Adachi, K Yashiro, R Sakuma, H Shiratori

    AMERICAN JOURNAL OF MEDICAL GENETICS   2001年7月

     詳細を見る

    記述言語:英語  

    Left-right asymmetric signaling molecules in mammals include three transforming growth factor beta (TGF beta)-related factors, Nodal, Lefty1 and Lefty2. They are all expressed on the left half of developing mouse embryos. Nodal acts as a left-side determinant by transducing signals through Smad and FAST and by inducing Pitx2 expression on the left side. Lefty proteins are antagonists that inhibit Nodal signaling. There are positive and negative transcriptional regulatory loops between nodal and lefty2 genes. Thus, Nodal activates its own gene and lefty2, Lefty2 protein produced then inhibits Nodal signaling and terminates expression of both genes. This feedback mechanism can restrict the range and duration of Nodal signaling in developing embryos, (C) 2001 Wiley-Liss, Inc.

所属学協会

  • 日本分子生物学会

教育活動概要

  • 以下の講義を担当・分担している。

    生命の科学A(基幹教育科目)、基礎生物学(医学部2年生)、発生学(医学部2年生)、発生生物学 (生命科学科3年生)、人体構造と機能I(医学府修士)、分子医学概論(医療経営・管理学専攻)、他

    研究・実習では、研究室配属、卒業研究の指導、大学院生の指導を行っている。

担当授業科目

  • 人体構造と機能Ⅰ

    2024年4月 - 2024年6月   春学期

  • 生命の科学A

    2024年4月 - 2024年6月   春学期

  • 発生生物学

    2023年10月 - 2024年3月   後期

  • 発生学

    2023年10月 - 2024年3月   後期

  • 生命科学研究入門

    2023年10月 - 2024年3月   後期

  • 人体構造と機能Ⅰ

    2023年4月 - 2023年9月   前期

  • 分子医学概論

    2023年4月 - 2023年9月   前期

  • 基礎生物学

    2023年4月 - 2023年9月   前期

  • 研究室配属

    2023年4月 - 2023年9月   前期

  • 生命科学研究入門

    2022年10月 - 2023年3月   後期

  • 発生学

    2022年10月 - 2023年3月   後期

  • 発生生物学

    2022年10月 - 2023年3月   後期

  • 研究室配属

    2022年4月 - 2022年9月   前期

  • 分子医学概論

    2022年4月 - 2022年9月   前期

  • 人体構造と機能Ⅰ

    2022年4月 - 2022年9月   前期

  • 基礎生物学

    2022年4月 - 2022年9月   前期

  • 生命科学研究入門

    2021年10月 - 2022年3月   後期

  • 発生学

    2021年10月 - 2022年3月   後期

  • 発生生物学

    2021年10月 - 2022年3月   後期

  • 研究室配属

    2021年4月 - 2021年9月   前期

  • 分子医学概論

    2021年4月 - 2021年9月   前期

  • 医学研究特論 I

    2021年4月 - 2021年9月   前期

  • 基礎生物学

    2021年4月 - 2021年9月   前期

  • 人体構造と機能Ⅰ

    2021年4月 - 2021年9月   前期

  • 発生生物学

    2020年10月 - 2021年3月   後期

  • 生命の科学A

    2020年10月 - 2021年3月   後期

  • 生命科学研究入門

    2020年10月 - 2021年3月   後期

  • 発生学

    2020年10月 - 2021年3月   後期

  • 研究室配属

    2020年4月 - 2020年9月   前期

  • 基礎生物学

    2020年4月 - 2020年9月   前期

  • 人体構造と機能Ⅰ

    2020年4月 - 2020年9月   前期

  • 分子医学概論

    2020年4月 - 2020年9月   前期

  • 発生生物学

    2019年10月 - 2020年3月   後期

  • 生命科学研究入門

    2019年10月 - 2020年3月   後期

  • 発生学

    2019年10月 - 2020年3月   後期

  • 人体構造と機能Ⅰ

    2019年4月 - 2019年9月   前期

  • 分子医学概論

    2019年4月 - 2019年9月   前期

  • 研究室配属

    2019年4月 - 2019年9月   前期

  • 生命科学研究入門

    2018年10月 - 2019年3月   後期

  • 発生学

    2018年10月 - 2019年3月   後期

  • 発生生物学

    2018年10月 - 2019年3月   後期

  • 人体構造と機能Ⅰ

    2018年4月 - 2018年9月   前期

  • 分子医学概論

    2018年4月 - 2018年9月   前期

  • 研究室配属(医学科3年生)

    2018年4月 - 2018年9月   前期

  • 発生学

    2017年10月 - 2018年3月   後期

  • 生命科学研究入門

    2017年10月 - 2018年3月   後期

  • 発生生物学

    2017年10月 - 2018年3月   後期

  • 人体構造と機能I

    2017年4月 - 2017年9月   前期

  • 医学研究特論

    2017年4月 - 2017年9月   前期

  • 研究室配属(医学科3年生)

    2017年4月 - 2017年9月   前期

  • 分子医学概論

    2017年4月 - 2017年9月   前期

  • 人体構造学概論

    2017年4月 - 2017年9月   前期

  • 生命の科学A

    2017年4月 - 2017年6月   春学期

  • 発生学

    2016年10月 - 2017年3月   後期

  • 生命科学研究入門

    2016年10月 - 2017年3月   後期

  • 発生生物学

    2016年10月 - 2017年3月   後期

  • 生命の科学A

    2016年4月 - 2016年9月   前期

  • 研究室配属(医学科3, 6年生)

    2016年4月 - 2016年9月   前期

  • 分子医学概論

    2016年4月 - 2016年9月   前期

  • 人体構造と機能I

    2016年4月 - 2016年9月   前期

  • 人体構造学概論

    2016年4月 - 2016年9月   前期

  • 発生生物学

    2015年10月 - 2016年3月   後期

  • 生命科学研究入門

    2015年10月 - 2016年3月   後期

  • 発生学

    2015年10月 - 2016年3月   後期

  • 医学研究特論I

    2015年4月 - 2015年9月   前期

  • 研究室配属(医学科、生命科学科3年生)

    2015年4月 - 2015年9月   前期

  • 分子医学概論

    2015年4月 - 2015年9月   前期

  • 人体構造学概論

    2015年4月 - 2015年9月   前期

  • 人体構造と機能I

    2015年4月 - 2015年9月   前期

  • 発生学

    2014年10月 - 2015年3月   後期

  • 総合医学III

    2014年10月 - 2015年3月   後期

  • 分子細胞生物学II

    2014年10月 - 2015年3月   後期

  • 生命の科学A

    2014年4月 - 2014年9月   前期

  • 人体構造と機能I

    2014年4月 - 2014年9月   前期

  • 研究室配属(医学科3, 6年生)

    2014年4月 - 2014年9月   前期

  • 分子医学概論

    2014年4月 - 2014年9月   前期

  • 人体構造学概論

    2013年10月 - 2014年3月   後期

  • 総合医学III

    2013年10月 - 2014年3月   後期

  • 分子細胞生物学II

    2013年10月 - 2014年3月   後期

  • 発生学

    2013年10月 - 2014年3月   後期

  • 医学生物学概論

    2013年10月 - 2014年3月   後期

  • コアセミナー

    2013年4月 - 2013年9月   前期

  • 医学研究特論I

    2013年4月 - 2013年9月   前期

  • 研究室配属(医学科3, 6年生)

    2013年4月 - 2013年9月   前期

  • 分子医学概論

    2013年4月 - 2013年9月   前期

  • 人体構造と機能I

    2013年4月 - 2013年9月   前期

  • 人体構造学概論

    2012年10月 - 2013年3月   後期

  • 総合医学III

    2012年10月 - 2013年3月   後期

  • 分子細胞生物学II

    2012年10月 - 2013年3月   後期

  • 発生学

    2012年10月 - 2013年3月   後期

  • 医学生物学概論

    2012年10月 - 2013年3月   後期

  • コアセミナー

    2012年4月 - 2012年9月   前期

  • 研究室配属(医学科3年生)

    2012年4月 - 2012年9月   前期

  • 分子医学概論

    2012年4月 - 2012年9月   前期

  • 人体構造と機能I

    2012年4月 - 2012年9月   前期

  • 人体構造学概論

    2011年10月 - 2012年3月   後期

  • 総合医学III

    2011年10月 - 2012年3月   後期

  • 分子細胞生物学II

    2011年10月 - 2012年3月   後期

  • 発生学

    2011年10月 - 2012年3月   後期

  • 医学生物学概論

    2011年10月 - 2012年3月   後期

  • コアセミナー

    2011年4月 - 2011年9月   前期

  • 研究室配属(医学科3年生)、早期研究室体験実習(生命科学科)

    2011年4月 - 2011年9月   前期

  • 研究室配属(医学科6年生)

    2011年4月 - 2011年9月   前期

  • 分子医学概論

    2011年4月 - 2011年9月   前期

  • 人体構造と機能I

    2011年4月 - 2011年9月   前期

  • 人体構造学概論

    2010年10月 - 2011年3月   後期

  • 生物科学I

    2010年10月 - 2011年3月   後期

  • 総合医学III

    2010年10月 - 2011年3月   後期

  • 分子細胞生物学II

    2010年10月 - 2011年3月   後期

  • 発生学

    2010年10月 - 2011年3月   後期

  • 医学生物学概論

    2010年10月 - 2011年3月   後期

  • コアセミナー

    2010年4月 - 2010年9月   前期

  • 研究室配属(医学科3年生)

    2010年4月 - 2010年9月   前期

  • 研究室配属(医学科6年生)

    2010年4月 - 2010年9月   前期

  • 分子医学概論

    2010年4月 - 2010年9月   前期

  • 人体構造と機能I

    2010年4月 - 2010年9月   前期

  • 人体構造学概論

    2009年10月 - 2010年3月   後期

  • 総合医学III

    2009年10月 - 2010年3月   後期

  • 分子細胞生物学II

    2009年10月 - 2010年3月   後期

  • 発生学

    2009年10月 - 2010年3月   後期

  • 医学生物学概論

    2009年10月 - 2010年3月   後期

  • コアセミナー

    2009年4月 - 2009年9月   前期

  • 研究室配属(医学科3年生)、早期研究室体験実習(生命科学科)

    2009年4月 - 2009年9月   前期

  • 分子医学概論

    2009年4月 - 2009年9月   前期

  • 人体構造と機能I

    2009年4月 - 2009年9月   前期

  • 人体構造学概論

    2008年10月 - 2009年3月   後期

  • 総合医学III

    2008年10月 - 2009年3月   後期

  • 基礎研究者養成科目(実習)

    2008年10月 - 2009年3月   後期

  • 発生学

    2008年10月 - 2009年3月   後期

  • 医学生物学概論

    2008年10月 - 2009年3月   後期

  • コアセミナー

    2008年4月 - 2008年9月   前期

  • 分子医学概論

    2008年4月 - 2008年9月   前期

  • 人体構造と機能I

    2008年4月 - 2008年9月   前期

  • 基礎研究者養成科目(実習)

    2007年10月 - 2008年3月   後期

  • 人体構造学概論

    2007年10月 - 2008年3月   後期

  • 医学生物学概論

    2007年10月 - 2008年3月   後期

  • 発生学

    2007年10月 - 2008年3月   後期

  • 分子医学概論

    2007年4月 - 2007年9月   前期

  • コアセミナー

    2007年4月 - 2007年9月   前期

  • 人体構造と機能I

    2007年4月 - 2007年9月   前期

  • 発生学

    2006年10月 - 2007年3月   後期

  • 人体構造学概論

    2006年10月 - 2007年3月   後期

  • 医学生物学概論

    2006年10月 - 2007年3月   後期

  • コアセミナー

    2006年4月 - 2006年9月   前期

  • 細胞シグナル伝達

    2006年4月 - 2006年9月   前期

  • 人体構造と機能I

    2006年4月 - 2006年9月   前期

  • 基礎医学入門

    2006年4月 - 2006年9月   前期

  • 医学生物学概論

    2005年10月 - 2006年3月   後期

▼全件表示