Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis
Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis
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雄激素调节生殖器官发生中的二态性 F-肌动蛋白组装
DOI：
10.1159/000477452
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发表时间：
2017
影响因子：
2.3
通讯作者：
Yamada Gen
中科院分区：
文献类型：
--
作者：
Liu Liqing;Suzuki Kentaro;Chun Eunice;Murashima Aki;Sato Yuki;Nakagata Naomi;Fujimori Toshihiko;Yonemura Shigenobu;He Wanzhong;Yamada Gen
雄激素活性受损会导致男性生殖道性分化缺陷，包括尿道下裂，这是一种阴茎尿路的异常形成。尿路间充质细胞(UMCs)中的雄激素信号在驱动二相性尿路发育中起着重要作用。然而，性分化的细胞事件实际上仍然未知。本研究通过组织学分析、荧光染色和透射电子显微镜观察，揭示了UMCs的细胞二型性。通过时间推移成像进一步分析F-肌动蛋白动力学和UMCs迁移行为。我们观察到，在女性UMCs中，F-肌动蛋白显著积聚，细胞外基质(ECM)组装不良。相反，在男性UMCs中，F-肌动蛋白通过膜受体与ECM共同排列的细小纤维被发现。在雄激素调节的男性化编程窗口中，在时间上确定了二态F-肌动蛋白组装的过程，并在空间上分布在几个胚胎生殖组织中。时间推移分析也证明了雄激素对UMCS中F-肌动蛋白性别模式的阶段性调节。此外，雄激素还调节UMCs的协调迁移。这些结果表明，雄激素信号调节F-肌动蛋白从细胞质聚集到膜纤维的组装。这种改变似乎促进了细胞外基质的组装和UMCs的移动，有助于男性生殖器官的发生。
Impaired androgen activity induces defective sexual differentiation of the male reproductive tract, including hypospadias, an abnormal formation of the penile urethra. Androgen signaling in the urethral mesenchyme cells (UMCs) plays essential roles in driving dimorphic urethral development. However, cellular events for sexual differentiation remain virtually unknown. In this study, histological analyses, fluorescent staining, and transmission electron microscopy (TEM) were performed to reveal the cellular dimorphisms of UMCs. F-actin dynamics and migratory behaviors of UMCs were further analyzed by time-lapse imaging. We observed a prominent accumulation of F-actin with poorly assembled extracellular matrix (ECM) in female UMCs. In contrast, thin fibrils of F-actin co-aligning with the ECM through membrane receptors were identified in male UMCs. Processes for dimorphic F-actin assemblies were temporally identified during an androgen-regulated masculinization programming window and spatially distributed in several embryonic reproductive tissues. Stage-dependent modulation of the F-actin sexual patterns by androgen in UMCs was also demonstrated by time-lapse analysis. Moreover, androgen regulates coordinated migration of UMCs. These results suggest that androgen signaling regulates the assembly of F-actin from cytoplasmic accumulation to membranous fibrils. Such alteration appears to promote the ECM assembly and the mobility of UMCs, contributing to male type genital organogenesis.
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DOI：
10.1159/000147794
发表时间：
1996
期刊：
Acta anatomica
影响因子：
--
作者：
Simon W. Hayward;Laurence S. Baskin;Peter C. Haughney;A. Cunha;B. A. Foster;Rajvir Dahiya;G. Prins;Cunha Gr
通讯作者：
Simon W. Hayward;Laurence S. Baskin;Peter C. Haughney;A. Cunha;B. A. Foster;Rajvir Dahiya;G. Prins;Cunha Gr
影响因子：
1.5
作者：
Abe, Takaya;Kiyonari, Hiroshi;Fujimori, Toshihiko
通讯作者：
Fujimori, Toshihiko
DOI：
10.1159/000363609
发表时间：
2014-01-01
期刊：
UNDERSTANDING DIFFERENCES AND DISORDERS OF SEX DEVELOPMENT (DSD)
影响因子：
--
作者：
Welsh, Michelle;Suzuki, Hiroko;Yamada, Gen
通讯作者：
Yamada, Gen
影响因子：
2.8
作者：
McDonald, Kent L.
通讯作者：
McDonald, Kent L.