@article{3bcdf503377648fd950d18fbbf298c3d,
title = "Androgen-regulated MafB drives cell migration via MMP11-dependent extracellular matrix remodeling in mice",
abstract = "While androgen is considered a pivotal regulator of sexually dimorphic development, it remains unclear how it orchestrates the differentiation of reproductive organs. Using external genitalia development as a model, we showed that androgen, through the transcription factor MafB, induced cell migration by remodeling the local extracellular matrix (ECM), leading to increased cell contractility and focal adhesion assembly. Furthermore, we identified the matrix metalloproteinase Mmp11 as a MafB target gene under androgen signaling. MMP11 remodels the local ECM environment by degrading Collagen VI (ColVI). The reduction of ColVI led to the fibrillar deposition of fibronectin in the MafB-expressing bilateral mesenchyme both in vivo and ex vivo. The ECM remodeling and development of migratory cell characteristics were lost in the MafB loss-of-function mice. These results demonstrate the requirement of mesenchymal-derived androgen signaling on ECM-dependent cell migration, providing insights into the regulatory cellular mechanisms underlying androgen-driven sexual differentiation.",
keywords = "Biological sciences, cell biology, molecular biology",
author = "Alcantara, {Mellissa C.} and Kentaro Suzuki and Acebedo, {Alvin R.} and Daiki Kajioka and Satoshi Hirohata and Tsuneyasu Kaisho and Yu Hatano and Kazuo Yamagata and Satoru Takahashi and Gen Yamada",
note = "Funding Information: We would like to thank Dr. Suneel Apte and Dr. Timothy Mead of the Lerner's Research Institute; the Laboratory Animal Center, the Department of Immunology, and the Central Research Facility of the Wakayama Medical University; and Mr. Ryouya Taniguchi of Kindai University for their advice and technical support. We would also like to acknowledge Tomiko Iba, Yugi Rim, and the members of the Department of Developmental Genetics for their invaluable support. This work was supported by the Japan Society for the Promotion of Science KAKENHI (17H06432, 18K06837, 18K06938, 21K06822, and 21K19538) and the Monbukagakusho Scholarship from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. Conceptualization: K.S. and G.Y.; methodology: M.C.A. K.S. and A.R.A.; investigation: M.C.A. D.K. and Y.H.; writing – original draft, visualization: M.C.A.; writing – review and editing: K.S. and G.Y.; resources: S.H. T.K. K.Y. and S.T.; supervision: K.S. and G.Y.; funding acquisition: K.S. and G.Y. The authors have nothing to declare. We support inclusive, diverse, and equitable conduct of research. Funding Information: We would like to thank Dr. Suneel Apte and Dr. Timothy Mead of the Lerner{\textquoteright}s Research Institute; the Laboratory Animal Center, the Department of Immunology, and the Central Research Facility of the Wakayama Medical University; and Mr. Ryouya Taniguchi of Kindai University for their advice and technical support. We would also like to acknowledge Tomiko Iba, Yugi Rim, and the members of the Department of Developmental Genetics for their invaluable support. This work was supported by the Japan Society for the Promotion of Science KAKENHI ( 17H06432 , 18K06837 , 18K06938 , 21K06822 , and 21K19538 ) and the Monbukagakusho Scholarship from the Japanese Ministry of Education , Culture, Sports, Science, and Technology. Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = dec,
day = "22",
doi = "10.1016/j.isci.2022.105609",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "12",
}