Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice

Alvin R. Acebedo, Kentaro Suzuki, Shinjiro Hino, Mellissa C. Alcantara, Yuki Sato, Hisashi Haga, Ken ichi Matsumoto, Mitsuyoshi Nakao, Kenji Shimamura, Toru Takeo, Naomi Nakagata, Shinichi Miyagawa, Ryuichi Nishinakamura, Robert S. Adelstein, Gen Yamada

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Abstract

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.

Original languageEnglish
Article number95
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

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    Acebedo, A. R., Suzuki, K., Hino, S., Alcantara, M. C., Sato, Y., Haga, H., Matsumoto, K. I., Nakao, M., Shimamura, K., Takeo, T., Nakagata, N., Miyagawa, S., Nishinakamura, R., Adelstein, R. S., & Yamada, G. (2019). Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice. Communications Biology, 2(1), [95]. https://doi.org/10.1038/s42003-019-0336-3