1Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, 641-8509 Japan.
2Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, 860-0811 Japan.
Commun Biol. 2019 Mar 8;2:95. doi: 10.1038/s42003-019-0336-3. eCollection 2019.
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.
哺乳动物胚胎外生殖器（eExG）的形态发生在雄性和雌性之间表现出动态差异。在基因型雄性中，eExG 会对雄激素信号做出反应而雄性化。这一过程的破坏会导致多种雄性生殖器官缺陷。目前，雄激素驱动的性器官形态发生的机制尚不清楚。我们在这里表明，由 MYH10 介导的间质衍生的肌动球蛋白收缩对于小鼠 eExG 的雄性化是必不可少的。MYH10 在雄性 eExG 的双侧间质中表达明显。雄激素诱导双侧间质中 MYH10 蛋白表达和肌动球蛋白收缩。通过 blebbistatin 处理抑制肌动球蛋白收缩和间质遗传缺失会导致尿道雄性化缺陷，伴有间质凝聚减少。我们还提出，肌动球蛋白收缩调节雄激素依赖性间质定向细胞迁移，形成双侧间质中的凝聚，从而改变尿道板形状，完成尿道雄性化。因此，间质衍生的肌动球蛋白收缩对于雄激素驱动的尿道雄性化是必不可少的。
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