| 1. |
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, Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation, Cell Mol Immunol., 10.1038/s41423-020-00559-7, 2020.10. |
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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, Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice, Scientific reports, 10.1038/s41598-019-48321-y, 9, 1, 2019.12, 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.. |
| 3. |
北島 桂子, Chikara Meno, Leukotriene B4 receptor type 2 (BLT2) enhances skin barrier function by regulating tight junction proteins., 10.1096/fj, 30, 2, 933-947, 2016.02, 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. Leukot. |
| 4. |
北島 桂子, Chikara Meno, Shinya Oki, Hyperglycemia impairs left-right axis formation and thereby disturbs heart morphogenesis in mouse embryos., 10.1073/pnas., 112, .8, E5300-E5307, 2015.10, 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 t. |
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北島 桂子, 角 智行, 沖 真弥, 大川 恭行, 目野 主税, Wnt signaling regulates left-right axis formation in the node of mouse embryos., Developmental Biology, 10.1016/j.ydbio.2013.05.011, 380, 2, 222-232, 2013.08, 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.. |
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Noda T, Oki S, Kitajima K, Harada T, Komune S, Meno C., Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo., Developmental Biology, 362, 1, 83-93, 2012.02, 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.. |
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角 智行, 沖 真弥, 北島 桂子, 目野 主税, Epiblast ground state is controlled by canonical Wnt/β-catenin signaling in the postimplantation mouse embryo and epiblast stem cells., PLos One, 10.1371/journal.pone.0063378, 8, 5, e63378, 2013.05, 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.. |
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Sanematsu F, Hirashima M, Laurin M, Takii R, Nishikimi A, Kitajima K, Ding G, Noda M, Murata Y, Tanaka Y, Masuko S, Suda T, Meno C, Côté JF, Nagasawa T, Fukui Y., DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4., Circulation Research, 10.1161/CIRCRESAHA.110.223388, 107, 9, 1102-1105, 2010.09. |
| 9. |
Oki S, Kitajima K, Meno C., Dissecting the role of Fgf signaling during gastrulation and left-right axis formation in mouse embryos using chemical inhibitors., Developmental Dynamics, 10.1002/dvdy.22282, 239, 6, 1768-1778, 2010.06. |
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Oki S., Kitajima K., Marques S., Belo JA., Yokoyama T., Hamada H., Meno C., Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos., Development, 136, 23, 3917-3925, 2009.12. |
