TY - JOUR
T1 - Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice
AU - Acebedo, Alvin R.
AU - Suzuki, Kentaro
AU - Hino, Shinjiro
AU - Alcantara, Mellissa C.
AU - Sato, Yuki
AU - Haga, Hisashi
AU - Matsumoto, Ken ichi
AU - Nakao, Mitsuyoshi
AU - Shimamura, Kenji
AU - Takeo, Toru
AU - Nakagata, Naomi
AU - Miyagawa, Shinichi
AU - Nishinakamura, Ryuichi
AU - Adelstein, Robert S.
AU - Yamada, Gen
N1 - Funding Information:
We thank Drs. B. Renfree, A. A. Thomson, T. Fujimori, R. M. Kypta, A. Pask, J. Hatakeyama, H. Takemoto, L. Liqing, D. Kajioka, L. A. Ipulan-Colet, S. Matsushita, A. Nukuda, Y. Takeda, and E. Chun for their invaluable support and T. Iba for her assistance. This work was supported by the Japan Society for the Promotion of Science KAKENHI Grant Numbers 17H06432, 18H02474, 18K06837, 18K06938, the program of the Joint Usage/Research Center for Developmental Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University and by the Monbukagusho scholarship, Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects. Currently, mechanisms of androgen-driven sexually dimorphic organogenesis are still unclear. We show here that mesenchymal-derived actomyosin contractility, by MYH10, is essential for the masculinization of mouse eExG. MYH10 is expressed prominently in the bilateral mesenchyme of male eExG. Androgen induces MYH10 protein expression and actomyosin contractility in the bilateral mesenchyme. Inhibition of actomyosin contractility through blebbistatin treatment and mesenchymal genetic deletion induced defective urethral masculinization with reduced mesenchymal condensation. We also suggest that actomyosin contractility regulates androgen-dependent mesenchymal directional cell migration to form the condensation in the bilateral mesenchyme leading to changes in urethral plate shape to accomplish urethral masculinization. Thus, mesenchymal-derived actomyosin contractility is indispensable for androgen-driven urethral masculinization.
AB - The morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects. Currently, mechanisms of androgen-driven sexually dimorphic organogenesis are still unclear. We show here that mesenchymal-derived actomyosin contractility, by MYH10, is essential for the masculinization of mouse eExG. MYH10 is expressed prominently in the bilateral mesenchyme of male eExG. Androgen induces MYH10 protein expression and actomyosin contractility in the bilateral mesenchyme. Inhibition of actomyosin contractility through blebbistatin treatment and mesenchymal genetic deletion induced defective urethral masculinization with reduced mesenchymal condensation. We also suggest that actomyosin contractility regulates androgen-dependent mesenchymal directional cell migration to form the condensation in the bilateral mesenchyme leading to changes in urethral plate shape to accomplish urethral masculinization. Thus, mesenchymal-derived actomyosin contractility is indispensable for androgen-driven urethral masculinization.
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U2 - 10.1038/s42003-019-0336-3
DO - 10.1038/s42003-019-0336-3
M3 - Article
C2 - 31924935
AN - SCOPUS:85071275696
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 95
ER -