Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yukiko Ogino Last modified date:2019.06.10

Associate Professor / Attached Promotive Center for International Education and Research of Agriculture / Faculty of Agriculture


Papers
1. Hitoshi Miyakawa, Minae Watanabe, Marina Araki, Yukiko Ogino, Shinichi Miyagawa, Taisen Iguchi, Juvenile hormone-independent function of Krüppel homolog 1 in early development of water flea Daphnia pulex, Insect Biochemistry and Molecular Biology, 10.1016/j.ibmb.2017.12.007, 93, 12-18, 2018.02.
2. Saki Tohyama, Yukiko Ogino, Anke Lange, Taijun Myosho, Tohru Kobayashi, Yu Hirano, Gen Yamada, Tomomi Sato, Norihisa Tatarazako, Charles R. Tyler, Taisen Iguchi, Shinichi Miyagawa, Establishment of estrogen receptor 1 (ESR1)-knockout medaka
ESR1 is dispensable for sexual development and reproduction in medaka, Oryzias latipes, Development Growth and Differentiation, 10.1111/dgd.12386, 59, 6, 552-561, 2017.08.
3. Ryohei Yatsu, Yoshinao Katsu, Satomi Kohno, Takeshi Mizutani, Yukiko Ogino, Yasuhiko Ohta, Jan Myburgh, Johannes H. van Wyk, Louis J. Guillette Jt., Shinich Miyagawa, Taisen Iguchi, Characterization of evolutionary trend in squamate estrogen receptor sensitivity., General and Comparative Endocrinology, doi: 10.1016/j.ygcen.2016.04.005., 238, 88-95, 2016.11.
4. Tatsuya Sakamoto, Madoka Yoshiki, Hideya Takahashi, Masayuki Yoshida, Yukiko Ogino, Toshitaka Ikeuchi, Tomoya Nakamachi, Norifumi Konno, Kouhei Matsuda, Hirotaka Sakamoto, Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish, Scientific Reports, 10.1038/srep37991, 6, 2016.11.
5. Saki Tohyama, Shinichi Miyagawa, Anke Lange, Yukiko Ogino, Takeshi Mizutani, Masaru Ihara, Hiroaki Tanaka, Norihisa Tatarazako, Tohru Kobayashi, Charles R. Tyler, Taisen Iguchi, Evolution of estrogen receptors in ray-finned fish and their comparative responses to estrogenic substances, Journal of Steroid Biochemistry and Molecular Biology, 10.1016/j.jsbmb.2015.12.009, 158, 189-197, 2016.04.
6. Eri Sumiya, Yukiko Ogino, Kenji Toyota, Hitoshi Miyakawa, Shinich Miyagawa, Taisen Iguchi, Neverland regulates embryonic moltings through the regulation of ecdysteroid synthesis in the water flea Daphnia magna, and may thus act as a target for chemical disruption of molting., Journal of Applied Toxicology, 10.1002/jat.3306., 2016.02.
7. Kenji Toyota, Chizue Hiruta, Yukiko Ogino, Shinichi Miyagawa, Tetsuro Okamura, Yuta Onishi, Norihisa Tatarazako, Taisen Iguchi, Comparative developmental staging of female and male water fleas daphnia pulex and daphnia magna during embryogenesis, Zoological Science, 10.2108/zs150116, 33, 1, 31-37, 2016.02.
8. Yukiko Ogino, Shigehiro Kuraku, Hiroshi Ishibashi, Hitoshi Miyakawa, Eri Sumiya, Shinichi Miyagawa, Hajime Matsubara, Gen yamada, Michael E. Baker, Taisen Iguchi, Neofunctionalization of androgen receptor by gain-of-function mutations in teleost fish lineage, Molecular Biology and Evolution, 33, 228-244, 2016.01.
9. Ryohei Yatsu, Shinichi Miyagawa, Satomi Kohno, Benjamin B. Parrott, Katsushi Yamaguchi, Yukiko Ogino, Hitoshi Miyakawa, Russell H. Lowers, Shuji Shigenobu, Louis J. GuilletteJr., Taisen Iguchi, RNA-seq analysis of the gonadal transcriptome during Alligator mississippiensis temperature-dependent sex determination and differentiation., BMC Genomics, doi: 10.1186/s12864-016-2396-9., 17, 77, 2016.01.
10. Ryohei Yatsu, Shinichi Miyagawa, Satomi Kohno, Shigeru Saito, Russell H. Lowers, Yukiko Ogino, Naomi Fukuta, Yoshinao Katsu, Yasuhiko Ohta, Makoto Tominaga, Louis J. Guillette Jr, Taisen Iguchi, TRPV4 associates environmental temperature and sex determination in the American alligator, Scientific Report, 10.1038/srep18581, 5, article NO.18581, 2015.12.
11. Shoko Matsushita, Kentaro Suzuki, Yukiko Ogino, Shinjiro Hino, Tetsuya Sato, Mikita Suyama, Takahiro Matsumoto, Akiko Omori, Satoshi Inoue, Gen Yamada, Androgen regulates Mafb expression through its 3’UTR during mouse urethral masculinization, Endocrinology, http://dx.doi.org/10.1210/en.2015-1586, 157, 2, 844-857, 2015.11.
12. Pete A. Bain, Anu Kumar, Yukiko Ogino, Taisen Iguchi, Nortestosterone-derived synthetic progestogens do not activate the progestogen receptor of Murray–Darling rainbowfish (Melanotaenia fluviatilis) but are potent agonists of androgen receptors alpha and beta, Aquatic Toxicology, 163, 97-101, 2015.06.
13. Saki Tohyama, Shinichi Miyagawa, Anke Lange, Yukiko Ogino, Takeshi Mizutani, Norihisa Tatarazako, Yoshinao Katsu, Masaru Ihara, Hiroaki Tanaka, Hiroshi Ishibashi, Tohru Kobayashi, Charles R. Tyler, Taisen Iguchi, Understanding the Molecular Basis for Differences in Responses of Fish Estrogen Receptor Subtypes to Environmental Estrogens, Environmental Science & Technology, 10.1021/acs.est.5b00704, 49, 12, 7439-7447, 2015.06.
14. Shinichi Miyagawa, Anke Lange, Saki Tohyama, Yukiko Ogino, Takeshi Mizutani, Tohru Kobayashi, Norihisa Tatarazako, Charles R. Tyler, Taisen Iguchi, Characterization of Oryzias latipes glucocorticoid receptors and their unique response to progestins, Journal of Applied Toxicology, 10.1002/jat.3020, 35, 3, 302-309, 2015.03.
15. Kenji Toyota, Hitoshi Miyakawa, Katsushi Yamaguchi, Shuji Shigenobu, Yukiko Ogino, Norihisa Tatarazako, Shinichi Miyagawa, Taisen Iguchi, NMDA receptor activation upstream of methyl farnesoate signaling for short day-induced male offspring production in the water flea, Daphnia pulex, BMC Genomics, 10.1186/s12864-015-1392-9, 16, 1, 2015.03.
16. Peter A. Bain, Yukiko Ogino, Shinichi Miyagawa, Taisen Iguchi, Anu Kumar, Differential ligand selectivity of androgen receptors α and β from Murray-Darling rainbowfish (Melanotaenia fluviatilis), Aquatic Toxicology, 212, 84-91, 2015.02.
17. Chizue Hiruta, Yukiko Ogino, Tetsushi Sakuma, Kenji Toyota, Shinichi Miyagawa, Takashi Yamamoto, Taisen Iguchi, Targeted gene disruption by use of transcription activator-like effector nuclease (TALEN) in the water flea Daphnia pulex, BMC Biotechnology, 14, 95, 2014.11.
18. AnthonySeb́illot, Pauliina Damdimopoulou, 荻野 由紀子, Petra Spirhanzlova, Shinichi Miyagawa, David Du Pasquier,, Nora Mouatassim, Taisen Iguchi, Gregory F. Lemkine, Barbara A. Demeneix, Andrew J. Tindall, Rapid Fluorescent Detection of (Anti)androgens with spiggin-gfp Medaka, Environmental Science & Technology, 48, 10919-10928, 2014.09.
19. Eri Sumiya, Yukiko Ogino, Hitoshi Miyakawa, Chizue Hiruta, Kenji Toyota, Shinichi Taisen, Taisen Iguchi, Roles of ecdysteroids for progression of reproductive cycle in the fresh water crustacean, Frontiers in Zoology, 11, 60, 2014.08.
20. Akiko Omori, Shinichi Miyagawa, Yukiko Ogino, Masayo Harada, Kenichiro Ishii, Yoshiki Sugimura, Hajime Ogino, Naomi Nakagata, Gen Yamada, Essential roles of epithelial bone morphogenetic protein signaling during prostatic development, Endocrinology, 155, 2534-2544, 2014.07.
21. Shinichi Miyagawa, Anke Lange, Ikumi Hirakawa, Saki Tohyama, Yukiko Ogino, Takeshi Mizutani, Yoshihiro Kagami, Teruhiko Kusano, Masaru Ihara, Hiroaki Tanaka, Norihisa Tatarazako, Yasuhiko Ohta, Yoshinao Katsu, Charles R. Tyler, Taisen Iguchi, Differing species responsiveness of estrogenic contaminants in fish is conferred by the ligand binding domain of the estrogen receptor, Environmental Science & Technology, 10.1021/es5002659, 48, 9, 5254-5263, 2014.05.
22. Harpreet Bhatia, Anupama Kumar, Yukiko Ogino, Adrienne Gregg, John Chapman, Mike J. McLaughlin, Taisen Iguchi, Di-n-butyl phthalate causes estrogenic effects in adult male Murray rainbowfish (Melanotaenia fluviatilis), Aquatic Toxicology, 10.1016/j.aquatox.2014.01.025, 149, 103-115, 2014.04.
23. Harpreet Bhatia, Anupama Kumar, Yukiko Ogino, Jun Do, Anrienne Gregg, John Chapman, Mike J. Mclaughlin, Taisen Iguchi, Effects of the commercial antiandrogen flutamide on the biomarkers of reproduction in male Murray rainbowfish (Melanotaenia fluviatilis),, Environmental Toxicology and Chemistry, 33, 1098-1107, 2014.03.
24. Yukiko Ogino, Ikumi Hirakawa, Keiji Inohaya, Eri Sumiya, Shinichi Miyagawa, Nancy Denslow, Gen Yamada, Norihisa Tatarazako, Taisen Iguchi, Bmp7 and Lef1 are the down stream effectors of androgen signaling in androgen-induced sex characteristics development in medaka, Endocrinology, 155, 449-462, 2014.02.
25. Tomohiro Oka, Naoko Mitsui-Watanabe, Norihisa Tatarazako, Yuta Onishi, Yoshinao Katsu, Shinichi Miyagawa, Yukiko Ogino, Ryohei Yatsu, Satomi Kohno, Minoru Takase, Yukio Kawashima, Yasuhiko Ohta, Yasunobu Aoki, Louis J. Guillette, Taisen Iguchi, Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors, Journal of Applied Toxicology, 10.1002/jat.2825, 33, 9, 991-1000, 2013.09, Thyroid hormones are essential for the regulation of a wide range of biological processes associated with normal development and metabolism in vertebrates. For the screening of chemicals with a potential thyroid hormone and anti-thyroid hormone activities, we have established transient transactivation assay systems using thyroid hormone receptors (TRα and TRβ) from three frog species (Xenopus laevis, Silurana tropicalis and Rana rugosa), a fish (Oryzias latipes), an alligator (Alligator mississippiensis) and a human (Homo sapiens). In all species examined, similar transcriptional activities were found for triiodothyronine (T3: 10-11 M in TRα and 10-10 M in TRβ) and thyroxine (T4: 10-9 M in TRα and 10-8 M in TRβ). Analogs of thyroid hormone (3,5,3′,-triiodothyroacetic acid and 3,3′,5,5′-tetraiodothyroacetic acid) exhibited weaker activity, requiring 10-fold higher concentrations for induction of activity when compared with T3 and T4. These results provide support for the usefulness of in vitro screening assay systems as part of an approach to test chemicals for potential thyroid hormone receptor activity. In addition, we observed that T3-stimulated transcriptional activity of the O. latipes TRα was inhibited by 10-5 M tetrabromobisphenol A (TBBPA). In contrast, TR antagonist activities on TRα were not encountered in other species, even with TBBPA concentrations at 10-5 M. In vitro transactivation assay systems using TRs from various species can be used for the screening of chemicals with thyroid-receptor agonist and antagonist activities. They also can be used for studies that examine evolutionary differences among species in the potency of TR activation..
26. M. Villacorte, K. Suzuki, A. Hirasawa, Yasuyuki Ohkawa, Mikita Suyama, T. Maruyama, D. Aoki, Yukiko Ogino, S. Miyagawa, T. Terabayashi, Y. Tomooka, N. Nakagata, G. Yamada, β-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation, Oncogene, 10.1038/onc.2012.376, 32, 29, 3477-3482, 2013.07, The Wnt/β-catenin signaling is essential for various organogenesis and is often implicated during tumorigenesis. Dysregulated β-catenin signaling is associated with the formation of endometrial adenocarcinomas (EACs), which is considered as the common form of endometrial cancer in women. In the current study, we investigate the downstream target of Wnt/β-catenin signaling in the uterine epithelia and the mechanism leading to the formation of endometrial hyperplasia. We report that conditional ablation and activation of β-catenin in the uterine epithelia lead to aberrant epithelial structures and endometrial hyperplasia formation, respectively. We demonstrate that β-catenin regulates Foxa2 with its candidate upstream region for the uterine epithelia. Furthermore, knockdown of Foxa2 leads to defects in cell cycle regulation, suggesting a possible function of Foxa2 in the control of cell proliferation. We also observe that β-catenin and Foxa2 expression levels are augmented in the human specimens of complex atypical endometrial hyperplasia, which is considered to have a greater risk of progression to EACs. Thus, our study indicates that β-catenin regulates Foxa2 expression, and this interaction is possibly essential to control cell cycle progression during endometrial hyperplasia formation. Altogether, the augmented expression levels of β-catenin and Foxa2 are essential features during the formation of endometrial hyperplasia..
27. Kenji Toyota, Yasuhiko Kato, Masaru Sato, Naomi Sugiura, Shinichi Miyagawa, Hitoshi Miyakawa, Hajime Watanabe, Shigeto Oda, Yukiko Ogino, Chizue Hiruta, Takeshi Mizutani, Norihisa Tatarazako, Susanne Paland, Craig Jackson, John K. Colbourne, Taisen Iguchi, Molecular cloning of doublesex genes of four cladocera (water flea) species, BMC Genomics, 10.1186/1471-2164-14-239, 14, 1, 2013.04, Background: The gene doublesex (dsx) is known as a key factor regulating genetic sex determination in many organisms. We previously identified two dsx genes (DapmaDsx1 and DapmaDsx2) from a freshwater branchiopod crustacean, Daphnia magna, which are expressed in males but not in females. D. magna produces males by parthenogenesis in response to environmental cues (environmental sex determination) and we showed that DapmaDsx1 expression during embryonic stages is responsible for the male trait development. The D. magna dsx genes are thought to have arisen by a cladoceran-specific duplication; therefore, to investigate evolutionary conservation of sex specific expression of dsx genes and to further assess their functions in the environmental sex determination, we searched for dsx homologs in four closely related cladoceran species.Results: We identified homologs of both dsx genes from, D. pulex, D. galeata, and Ceriodaphnia dubia, yet only a single dsx gene was found from Moina macrocopa. The deduced amino acid sequences of all 9 dsx homologs contained the DM and oligomerization domains, which are characteristic for all arthropod DSX family members. Molecular phylogenetic analysis suggested that the dsx gene duplication likely occurred prior to the divergence of these cladoceran species, because that of the giant tiger prawn Penaeus monodon is rooted ancestrally to both DSX1 and DSX2 of cladocerans. Therefore, this result also suggested that M. macrocopa lost dsx2 gene secondarily. Furthermore, all dsx genes identified in this study showed male-biased expression levels, yet only half of the putative 5' upstream regulatory elements are preserved in D. magna and D. pulex.Conclusions: The all dsx genes of five cladoceran species examined had similar amino acid structure containing highly conserved DM and oligomerization domains, and exhibited sexually dimorphic expression patterns, suggesting that these genes may have similar functions for environmental sex determination in cladocerans..
28. Erica K. Brockmeier, Yukiko Ogino, Taisen Iguchi, David S. Barber, Nancy D. Denslow, Effects of 17β-trenbolone on Eastern and Western mosquitofish (Gambusia holbrooki and G. affinis) anal fin growth and gene expression patterns, Aquatic Toxicology, 10.1016/j.aquatox.2012.12.007, 128-129, 163-170, 2013.03, The Eastern and Western mosquitofish (Gambusia holbrooki and G. affinis) are potential bioindicator organisms for endocrine disruptors. Male mosquitofish have an elongated anal fin (gonopodium) used for internal fertilization whose formation is driven by androgens. Normal female mosquitofish have a normal, rounded anal fin which undergoes elongation into a gonopodium structure when female mosquitofish are exposed to androgenic chemicals. Significant issues with using mosquitofish as a bioindicator include the lack of knowledge on how anal fin growth in females corresponds to endpoints relevant to biological integrity and the lack of information on the molecular pathways that regulate anal fin growth. The objectives of this study were to understand how androgen-induced anal fin elongation relates to changes in endpoints related to the female reproductive system and to understand how anal fin elongation occurs in androgen-exposed female mosquitofish. To achieve these objectives, adult female G. holbrooki were exposed to a vehicle control or one of three doses of the androgen 17β-trenbolone (TB) at nominal concentrations of 0.1, 1 or 10 μg TB/L. Anal fin measurements were taken and livers were used for quantitative polymerase chain reaction analysis of vitellogenin (vtg) mRNA expression at multiple time points. 10 μg TB/L induced anal fin elongation after 7 days of treatment (one-way ANOVA, p< 0.05) as did 0.1 and 1 μg TB/L at later time points (one-way ANOVA, p< 0.05). 10 μg TB/L significantly reduced hepatic vtg gene expression at all time points assessed (one-way ANOVA, p< 0.05). There was no correlation between anal fin elongation levels and vtg gene expression (Spearman's ρ, p> 0.05). In a separate experiment, female G. holbrooki and G. affinis were exposed to the vehicle control or 1 μg TB/L. Anal fins were used for qualitative gene expression analysis of the genes sonic hedgehog (shh), muscle segment homeobox C (msxC), and fibroblast growth factor receptor 1 (fgfr1) by in situ hybridization. Shh was expressed in the distal tip of the gonopodium while msxC and fgfr1 were more widely expressed along the same anal fin rays during androgen exposure. These data provide insight into the molecular pathways involved in anal fin elongation and pave the way for future work toward developing the mosquitofish into a bioindicator organism for endocrine disruptors..
29. Hitoshi Miyakawa, Kenji Toyota, Ikumi Hirakawa, Yukiko Ogino, Shinichi Miyagawa, Shigeto Oda, Norihisa Tatarazako, Toru Miura, John K. Colbourne, Taisen Iguchi, A mutation in the receptor Methoprene-tolerant alters juvenile hormone response in insects and crustaceans, Nature Communications, 10.1038/ncomms2868, 4, 2013, Juvenile hormone is an essential regulator of major developmental and life history events in arthropods. Most of the insects use juvenile hormone III as the innate juvenile hormone ligand. By contrast, crustaceans use methyl farnesoate. Despite this difference that is tied to their deep evolutionary divergence, the process of this ligand transition is unknown. Here we show that a single amino-acid substitution in the receptor Methoprene-tolerant has an important role during evolution of the arthropod juvenile hormone pathway. Microcrustacea Daphnia pulex and D. magna share a juvenile hormone signal transduction pathway with insects, involving Methoprene-tolerant and steroid receptor coactivator proteins that form a heterodimer in response to various juvenoids. Juvenile hormone-binding pockets of the orthologous genes differ by only two amino acids, yet a single substitution within Daphnia Met enhances the receptor's responsiveness to juvenile hormone III. These results indicate that this mutation within an ancestral insect lineage contributed to the evolution of a juvenile hormone III receptor system..
30. Ikumi Hirakawa, Shinichi Miyagawa, Yoshinao Katsu, Yoshihiro Kagami, Norihisa Tatarazako, Tohru Kobayashi, Teruhiko Kusano, Takeshi Mizutani, Yukiko Ogino, Takashi Takeuchi, Yasuhiko Ohta, Taisen Iguchi, Gene expression profiles in the testis associated with testis-ova in adult Japanese medaka (Oryzias latipes) exposed to 17α-ethinylestradiol, Chemosphere, 10.1016/j.chemosphere.2011.12.047, 87, 7, 668-674, 2012.05, The occurrence of oocytes in the testis (testis-ova) of several fish species is often associated with exposure of estrogenic chemicals. However, induction mechanisms of the testis-ova remain to be elucidated. To develop marker genes for detecting testis-ova in the testis, adult male medaka were exposed to nominal concentration of 100ngL -1 of 17α-ethinylestradiol (EE2) for 3-5weeks, and 800ng estradiol benzoate (EB) for 3weeks (experiment I), and a measured concentration of 20ngL -1 EE2 for 1-6weeks (experiment II). Histological analysis was performed for the testis, and microarray analyses were performed for the testis, liver and brain. Microarray analysis in the estrogen-exposed medaka liver showed vitellogenin and choriogenin as estrogen responsive genes. Testis-ova were induced in the testis after 4weeks of exposure to 100ngL -1 EE2, 3weeks of exposure to 800ngEB, and 6weeks of exposure to 20ngL -1 EE2. Microarray analysis of estrogen-exposed testes revealed up-regulation of genes related to zona pellucida (ZP) and the oocytes marker gene, 42Sp50. Using quantitative RT-PCR we confirmed that Zpc5 gene can be used as a marker for the detection of testis-ova in male medaka..
31. Anke Lange, Yoshinao Katsu, Shinichi Miyagawa, Yukiko Ogino, Hiroshi Urushitani, Tohru Kobayashi, Toshiaki Hirai, Janice A. Shears, Masaki Nagae, Jun Yamamoto, Yuta Ohnishi, Tomohiro Oka, Norihisa Tatarazako, Yasuhiko Ohta, Charles R. Tyler, Taisen Iguchi, Comparative responsiveness to natural and synthetic estrogens of fish species commonly used in the laboratory and field monitoring, Aquatic Toxicology, 10.1016/j.aquatox.2011.09.004, 109, 250-258, 2012.03, Exposure to estrogenic chemicals discharged into the aquatic environment has been shown to induce feminization in wild freshwater fish and although fish species have been reported to differ in their susceptibility for these effects, empirical studies that directly address this hypothesis are lacking. In this study, in vitro ERα activation assays were applied in a range of fish species used widely in chemical testing (including, zebrafish, fathead minnow, medaka) and/or as environmental monitoring species (including, roach, stickleback, carp) to assess their comparative responsiveness to natural (estrone, estradiol, estriol) and synthetic (17α-ethinylestradiol (EE2), diethylstilbestrol (DES)) estrogens. In vivo exposures to EE2 via the water (nominal 2 and 10. ng/L for 7 days) were also conducted for seven fish species to compare their responsiveness for hepatic vitellogenin (VTG) mRNA induction (an ER mediated response). Of the fish species tested, zebrafish ERα was found to be the most responsive and carp and stickleback ERα the least responsive to natural steroid estrogens. This was also the case for exposure to EE2 with an ERα-mediated response sensitivity order of zebrafish > medaka > roach > fathead minnow > carp > stickleback. For VTG mRNA induction in vivo, the order of species responsiveness was: rainbow trout (not tested in the ERα activation assays) > zebrafish > fathead minnow > medaka > roach > stickleback > carp. Overall, the responses to steroid estrogens in vitro via ERα compared well with those seen in vivo (VTG induction for exposure to EE2) showing in vitro screening of chemicals using fish ERα-mediated responses indicative of estrogenic responses (VTG induction) in vivo..
32. Liqing Liu, Kentaro Suzuki, Naomi Nakagata, Kenichiro Mihara, Daisuke Matsumaru, Yukiko Ogino, Kenta Yashiro, Hiroshi Hamada, Zhonghua Liu, Sylvia M. Evans, Cathy Mendelsohn, Gen Yamada, Retinoic Acid Signaling Regulates Sonic Hedgehog and Bone Morphogenetic Protein Signalings During Genital Tubercle Development, Birth Defects Research Part B - Developmental and Reproductive Toxicology, 10.1002/bdrb.20344, 95, 1, 79-88, 2012.02, Retinoic acid (RA) plays pivotal roles in organogenesis, and both excessive and reduced amounts of RA cause developmental abnormalities. Reproductive organs are susceptible to teratogen toxigenicity, and the genital tubercle (GT) is one such representative organ. The physiological function of endogenous RA signaling and the mechanisms of RA-induced teratogenicity are poorly understood during the GT development. The objective of this study is to understand the developmental and teratogenic roles of RA during GT development by analyzing genetically modified mouse models. We found dynamic patterns of gene expression for the RA-synthesizing enzyme, Raldh2, and for the RA-catabolizing enzyme, Cyp26b1, during GT development. Rarb, an indicator gene for RA signaling, starts its expression in the prospective corpus cavernosum penis and in the urethral plate epithelium (UE), which plays central roles during GT development. Excessive RA signaling in Cyp26b1-/- mutants leads to abnormal extents of cell proliferation and differentiation during GT development, and also upregulates expression of growth factor signalings. They include Sonic hedgehog (Shh) signaling and Bone morphogenetic protein (Bmp) signaling, which are expressed in the UE and its bilateral mesenchyme. RA signaling positively regulatesShh and Bmp4 expression during GT development as testified also by the experiment of RA administration and analyses of loss-of-function of RA signaling mutants. Thus, RA signaling is involved in the developmental cascade necessary for UE formation and GT development..
33. Yukiko Ogino, Shinichi Miyagawa, Hironori Katoh, Gail S. Prins, Taisen Iguchi, Gen Yamada, Essential functions of androgen signaling emerged through the developmental analysis of vertebrate sex characteristics, Evolution and Development, 13, 315-325, 2011.05.
34. Aki Murashima, Shinichi Miyagawa, Yukiko Ogino, Hisayo Nishida-Fukuda, Kimi Araki, Takahiro Matsumoto, Takehito Kaneko, Kazuya Yoshinaga, Ken Ichi Yamamura, Takeshi Kurita, Shigeaki Kato, Anne M. Moon, Gen Yamada, Essential roles of androgen signaling in Wolffian duct stabilization and epididymal cell differentiation, Endocrinology, 10.1210/en.2010-1121, 152, 4, 1640-1651, 2011.04, The epididymis is a male accessory organ and functions for sperm maturation and storage under the control of androgen. The development of the epididymis is also androgen dependent. The Wolffian duct (WD), anlagen of the epididymis, is formed in both male and female embryos; however, it is stabilized only in male embryos by testicular androgen. Androgen drives subsequent differentiation of the WD into the epididymis. Although the essential roles of androgen in WD masculinization and epididymal function have been established, little is known about cellular events regulated precisely by androgen signaling during these processes. It is also unclear whether androgen signaling, especially in the epithelia, has further function for epididymal epithelial cell differentiation. In this study we examined the cellular death and proliferation controlled by androgen signaling via the androgen receptor (AR) in WD stabilization. Analyses using AR knockout mice revealed that androgen signaling inhibits epithelial cell death in this process. Analysis of AP2α-Cre;ARflox/Y mice, in which AR function is deleted in the WD epithelium, revealed that epithelial AR is not required for the WD stabilization but is required for epithelial cell differentiation in the epididymis. Specifically, loss of epithelial AR significantly reduced expression of p63 that is essential for differentiation of basal cells in the epididymal epithelium. We also interrogated the possibility of regulation of the p63 gene (Trp63) by AR in vitro and found that p63 is a likely direct target of AR regulation..
35. Sho Ohta, Yukiko Ogino, Kentro Suzuki, Mika Kamimura, Katsuro Tachibana, Gen Yamada, Sonoporation for gene transfer into embryos, Cold Spring Harbor Protocols, 10.1101/pdb.prot5581, 6, 3, 2011.03.
36. Yukiko Ogino, Hironori Katoh, Shigehiro Kuraku, Gen Yamada, Evolutionary history and functional characterization of androgen receptor genes in jawed vertebrates, Endocrinology, 150, 5415-5427, 2009.12.
37. Sho Ohta, Kentaro Suzuki, Shinichi Miyagawa, Yukiko Ogino, Mylah Villacorte, Yoshihiro Wada, Gen Yamada, Sonoporation in developmental biology, Electroporation and Sonoporation in Developmental Biology, 10.1007/978-4-431-09427-2_27, 317-326, 2009, Recent, molecular biology techniques have accomplished a large contribution to developmental biology. Especially, gene transduction techniques are indispensable to study the roles of regulatory genes underlying embryogenesis. Replication-competent retroviruses, transfection with lipofection and an in ovo electroporation have been established as gene transduction techniques for embryos. (Yamada et al., 1997; Muramatsu et al., 1998; Fukuda et al., 2000; Iba, 2000; Nakamura et al., 2000). Particularly, in ovo electroporation for chick embryos has been recognized as a powerful method to efficiently induce exogenous genes into target cells or tissues, and it has been widely utilized to investigate their functions during embryonic development. Because the electric current tend to affect mainly the epithelial cells of the embryo, in ovo electroporation is suitable for the studies of neurogenesis and neuronal differentiation. In fact, large number of information relating to neuronal development has been brought from the studies using in ovo electroporation (Okafuji et al., 1999; Nakamura and Funahashi, 2001)..
38. Sho Ohta, Kentaro Suzuki, Yukiko Ogino, Shinichi Miyagawa, Aki Murashima, Daisuke Matsumaru, Gen Yamada, Gene transduction by sonoporation, Development Growth and Differentiation, 10.1111/j.1440-169X.2008.01026.x, 50, 6, 517-520, 2008.08, Gene transduction technologies are essential tools for understanding of gene functions or gene cascades underlying embryogenesis. In this review, we introduce a gene transduction method using microbubble and ultrasound (hereafter referred to as sonoporation). Sonoporation is carried out with relatively simple procedures and easily transduces genes into mesenchymal cells without significant damage to target tissues. Therefore, sonoporation is effective for gene transduction to study the molecular mechanisms of morphogenesis..
39. Hisayo Nishida, Shinichi Miyagawa, Daisuke Matsumaru, Yoshihiro Wada, Yoshihiko Satoh, Yukiko Ogino, Shinji Fukuda, Taisen Iguchi, Gen Yamada, Gene expression analyses on embryonic external genitalia
Identification of regulatory genes possibly involved in masculinization processes, Congenital Anomalies, 10.1111/j.1741-4520.2008.00180.x, 48, 2, 63-67, 2008.06, Androgen plays a crucial role in initiating and maintaining the expression of male sexual characteristics in mammals. In humans and mice, any defects along the pathway of androgen functions result in congenital urogenital abnormalities. The genital tubercle (GT), an anlage of the external genitalia, differentiates into a penis in males and a clitoris in females. Although masculinization of the external genitalia is androgen-dependent, the molecular pathway of its potential downstream genes is largely unclear. To identify the genes involved in mouse GT masculinization, we performed gene expression analyses, such as real-time quantitative polymerase chain reaction and section in situ hybridization analysis. From our studies we have identified candidate genes, Cyp1b1, Fkbp51 and MafB as potential androgen targets during mouse GT masculinization..
40. Hisayo Nishida, Shinichi Miyagawa, Maxence Vieux-Rochas, Monica Morini, Yukiko Ogino, Kentaro Suzuki, Naomi Nakagata, Hueng Sik Choi, Giovanni Levi, Gen Yamada, Positive regulation of steroidogenic acute regulatory protein gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis, Endocrinology, 10.1210/en.2007-1265, 149, 5, 2090-2097, 2008.05, Split hand/foot malformation (SHFM) is syndromic ectrodactyly often associated with mental retardation and/or craniofacial defects. Several clinical reports previously described urogenital dysplasia such as micropenis, hypospadias, and small testis in SHFM patients. Genetic lesions in the Dlx5 and Dlx6 (Dlx5/6) locus are associated with the human genetic disorder SHFM type 1. Although Dlx5/6 are expressed in the testis, their possible function of Dlx5/6 during testis differentiation has not been described. In this study, we show that Dlx5/6 are expressed in the fetal Leydig cells during testis development. We examined the effect of Dlx5 expression on the promoter activation of the steroidogenic acute regulatory protein (StAR) gene, which is essential for gonadal and adrenal steroidogenesis, in a Leydig cell line. Dlx5 efficiently activates the StAR promoter when GATA-4, another transcription factor essential for testicular steroidogenesis, was coexpressed. The transcriptional activation required the GATA-4-recognition element in the StAR promoter region and Dlx5 can physically interact with GATA-4. Furthermore, we herein show that the double inactivation of Dlx5 and Dlx6 in the mouse leads to decreased testosterone level and abnormal masculinization phenotype. These results suggest that Dlx5 and Dlx6 participate in the control of steroidogenesis during testis development. The findings of this study may open the way to analyze human congenital birth defects..
41. Hironori Katoh, Yukiko Ogino, Gen Yamada, Cloning and expression analysis of androgen receptor gene in chicken embryogenesis, FEBS Letters, 10.1016/j.febslet.2006.01.093, 580, 6, 1607-1615, 2006.03, We cloned a full-length androgen receptor (AR) cDNA from chicken (Gallus gallus) gonads. The cDNA sequence has an open reading frame of 2109 bp encoding 703 amino acids. The chicken AR (cAR) shares high homology with ARs from other species in its amino acid sequences, in particular DNA binding domain (DBD) and ligand binding domain (LBD). RT-PCR analysis revealed that cAR mRNA is expressed in several embryonic tissues of both sexes, and relatively higher expression was observed in left ovary compared with testis. The immunoreactive signal of AR was co-localized within the ovarian cell nucleus, while such nuclear localization was not detected in those of testis. To get insight on the possible role of androgen-AR signaling during gonadal development, non-steroidal AR antagonist, flutamide, was administrated in ovo. The treatment induced the disorganization of sex cords in ovarian cortex at day 12 of incubation. The effect was restored by testosterone co-treatment, implying the possibility that AR mediated signaling may be involved in ovarian morphogenesis. Furthermore, co-treatment of flutamide with estradiol-17β (E2) also restored the phenotype, suggesting androgen-AR signaling might activate aromatase expression that is necessary for estrogen synthesis. These findings suggest androgen-AR signaling might contribute to chicken embryonic ovarian development..
42. Hidenao Ogi, Kentaro Suzuki, Yukiko Ogino, Mika Kamimura, Mami Miyado, Xu Ying, Zunyi Zhang, Masanori Shinohara, Yiping Chen, Gen Yamada, Ventral abdominal wall dysmorphogenesis of Msx1/Msx2 double-mutant mice, Anatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology, 10.1002/ar.a.20180, 284, 1, 424-430, 2005.05, Msx1 and Msx2 genes encode the homeodomain transcription factors. Several gene knockout mice and expression studies suggest that they possess functionally redundant roles in embryogenesis. In this study, we revealed that Msx1 and Msx2 were expressed during ventral body wall formation in an overlapping manner. Msx1/Msx2 double-mutant mice displayed embryonic abdominal wall defects with disorganized muscle layers and connective tissues. These findings indicate that Msx1 and Msx2 play roles in concert during embryonic ventral abdominal wall formation..
43. Mami Kamikawa-Miyado, Hidenao Ogi, Yukiko Ogino, Hironori Katoh, Kentaro Suzuki, Masanori Uemura, Junzoh Kitoh, Sen Ichi Oda, Gen Yamada, The morphological and histological characters of the male external genitalia of the house musk shrew, Suncus murinus, Zoological Science, 10.2108/zsj.22.463, 22, 4, 463-468, 2005.04, External genitalia are the reproductive organs necessary for efficient copulation and internal fertilization in various mammalian species. Their morphogeneses display significant morphological and developmental differences among species. The house musk shrew, Suncus murinus (hereafter described as suncus) is a species of the order Insectivora, which has been considered as primitive and one of the earliest eutheria phylogenetically. Comparative anatomical analyses of phylogenetically different mammals will contribute to the better understanding of morphological diversity of external genitalia. This study performed various anatomical and histological analyses concerning the organization of the external genitalia of male suncus. It was shown that the external genitalia of suncus possessed a muscular structure, which we proposed as musculus ischiocavernosus dorsalis of suncus. The musculus ischiocavernosus dorsalis is originated from the inner surface of the tuber ischiadicum and was allocated adjacent to the corpus cavernosum penis. In addition, a pair of α-smooth muscle actin positive muscles was located bilaterally to the urethra. This unique morphology of the external genitalia of suncus males may provide a unique model system to investigate genital morphogenesis..
44. Yukiko Ogino, Hironori Katoh, Gen Yamada, Androgen dependent development of a modified anal fin, gonopodium, as a model to understand the mechanism of secondary sexual character expression in vertebrates, FEBS Letters, 10.1016/j.febslet.2004.08.046, 575, 1-3, 119-126, 2004.09, Male external genitalia show structural variations among species. Androgenic hormones are essential for the morphological specification of male type copulatory organs, while little is known about the developmental mechanisms of such secondary sexual characters. Western mosquitofish Gambusia affinis may offer a clue to the sexual differentiation researches, because they show a prominent masculine sexual character for appendage development, anal fin to gonopodium (GP) transition, and its formation could be induced in early juvenile fry by exogenously supplied androgens. We show that GP development is promoted by androgen dependent augmentation of sonic hedgehog (Shh) expression. Two AR cDNAs were cloned and identified as ARα and ARβ from western mosquitofish. Both ARs were predominantly expressed in the distal region of outgrowing anal fin rays. Exposure of fry to androgen caused anal fin outgrowth concomitant with the Shh induction in the distal anal fin ray epithelium. When AR signaling was inhibited by its antagonist flutamide in fry, the initial induction of the Shh was suppressed accompanying retarded anal fin outgrowth. Similar suppression of anal fin outgrowth was induced by treatment with cyclopamine, an inhibitor of Shh signaling. These observations indicate that androgen dependent Shh expression is required for anal fin outgrowth leading to the formation of a genital appendage, the GP in teleost fishes. Androgen-induced GP formation may provide insights into the expression mechanism regulating the specification of sexual features in vertebrates..
45. Kentaro Suzuki, Daniel Bachiller, Yi Ping P. Chen, Mami Kamikawa, Hidenao Ogi, Ryama Haraguchi, Yukiko Ogino, Yasuhiro Minami, Yuji Mishina, Kyung Ahn, E. Bryan Crenshaw, Gen Yamada, Regulation of outgrowth and apoptosis for the terminal appendage
External genitalia: Development by concerted actions of BMP signaling, Development (Cambridge), 10.1242/dev.00846, 130, 25, 6209-6220, 2003.12, Extra-corporal fertilization depends on the formation of copulatory organs: the external genitalia. Coordinated growth and differentiation of the genital tubercle (GT), an embryonic anlage of external genitalia, generates a proximodistally elongated structure suitable for copulation, erection, uresis and ejaculation. Despite recent progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes of external genitalia formation. Bone morphogenetic protein genes (Bmp genes) and their antagonists were spatiotemporally expressed during GT development. Exogenously applied BMP increased apoptosis of GT and inhibited its outgrowth. It has been shown that the distal urethral epithelium (DUE), distal epithelia marked by the Fgf8 expression, may control the initial GT outgrowth. Exogenously applied BMP4 downregulated the expression of Fgf8 and Wnt5a, concomitant with increased apoptosis and decreased cell proliferation of the GT mesenchyme. Furthermore, noggin mutants and Bmpr1a conditional mutant mice displayed hypoplasia and hyperplasia of the external genitalia respectively. noggin mutant mice exhibited downregulation of Wnt5a and Fgf8 expression with decreased cell proliferation. Consistent with such findings, Wnt5a mutant mice displayed GT agenesis with decreased cell proliferation. By contrast, Bmpr1a mutant mice displayed decreased apoptosis and augmented Fgf8 expression in the DUE associated with GT hyperplasia. These results suggest that some of the Bmp genes could negatively affect proximodistally oriented outgrowth of GT with regulatory functions on cell proliferation and apoptosis. The DUE region can be marked only until 14.0 dpc (days post coitum) in mouse development, while GT outgrowth continues thereafter. Possible signaling crosstalk among the whole distal GT regions were also investigated..
46. Kentaro Suzuki, Yukiko Ogino, Ryutaro Murakami, Yoshihiko Satoh, Daniel Bachiller, Gen Yamada, Embryonic development of mouse external genitalia
Insights into a unique mode of organogenesis, Evolution and Development, 10.1046/j.1525-142X.2002.01061.x, 4, 2, 133-141, 2002.06.
47. Yukiko Ogino, Kentaro Suzuki, Ryuma Haraguchi, Yoshihiko Satoh, Pascal Dolle, Gen Yamada, External genitalia formation
Role of fibroblast growth factor, retinoic acid signaling, and distal urethral epithelium, Annals of the New York Academy of Sciences, 948, 13-31, 2001.01.