FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation
FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation
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DOI：
10.1242/dev.040519
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发表时间：
2010-01-15
期刊：
影响因子：
4.6
通讯作者：
Kanai, Yoshiakira
中科院分区：
文献类型：
--
作者：
Hiramatsu, Ryuji;Harikae, Kyoko;Kanai, Yoshiakira
在小鼠胚胎发生过程中，Sry 沿着发育中的 XY 性腺的前后 (AP) 轴以从中心到极的波状方式短暂激活。然而，Sry 表达下游睾丸起始通路从中心到极扩展的机制和意义仍不清楚。在这里，我们证明 FGF9 可以作为睾丸分化早期阶段管状发生程序向极地扩展的扩散导体。在性交后 11.0-11.25 天的前极、中极和后极的 XY 生殖嵴培养物中，尽管与中央区域隔离，但在前极和后极节中仍然观察到 Sry 及其靶基因 Sox9 的雄性特异性激活。然而，Sox9 的高水平表达未能维持，导致大多数极段睾丸索组织失败。使用 ROSA: lacZ 中段的重建实验显示，两极的管状缺陷得到了挽救，而 lacZ 阳性性腺实质细胞没有任何明显的贡献。分区培养测定还表明，性腺中心区域分泌的可溶性/扩散因子可能对两极的正常肾小管发生有贡献。在各种信号转导因子中，前极段和后极段的 Fgf9 表达均显着低于中央域。中央结构域的支持作用可以被外源性 FGF9 供应所取代，而 Wnt4 活性的降低并不能挽救极段的管状发生缺陷。这些观察结果表明，从中心到极点的 FGF9 扩散引导睾丸生成程序沿着发育中的 XY 性腺的 AP 轴向极地扩展。
In mouse embryogenesis, Sry is transiently activated in a center-to-pole wavelike manner along the anteroposterior (AP) axis of developing XY gonads. However, the mechanism and significance of the center-to-pole expansion of testis initiation pathways downstream of Sry expression remain unclear. Here we demonstrate that FGF9 can act as a diffusible conductor for a poleward expansion of tubulogenic programs at early phases of testis differentiation. In XY genital ridge cultures of anterior, middle and posterior segments at 11.0-11.25 days post-coitum, male-specific activation of Sry and its target gene, Sox9, was still observed in both anterior and posterior pole segments despite their isolation from the central domain. However, high-level Sox9 expression was not maintained, resulting in the failure of testis cord organization in most pole segments. A reconstruction experiment using ROSA: lacZ middle segments showed rescue of the tubulogenic defect in the poles without any appreciable contribution of lacZ-positive gonadal parenchyma cells. A partition culture assay also showed a possible contribution of soluble/diffusible factors secreted from the gonadal center domain to proper tubulogenesis in the poles. Among various signaling factors, Fgf9 expression was significantly lower in both anterior and posterior pole segments than in the central domain. The supportive role of the central domain could be substituted by exogenous FGF9 supply, whereas reduction of Wnt4 activity did not rescue the tubulogenesis defect in the pole segments. These observations imply that center-to-pole FGF9 diffusion directs a poleward expansion of testiculogenic programs along the AP axis of developing XY gonads.