Temporal and spatial dissection of Shh signaling in genital tubercle development
Temporal and spatial dissection of Shh signaling in genital tubercle development
复制标题
DOI：
10.1242/dev.039768
复制
发表时间：
2009-12-01
期刊：
影响因子：
4.6
通讯作者：
Ma, Liang
中科院分区：
文献类型：
--
作者：
Lin, Congxing;Yin, Yan;Ma, Liang
生殖器结节（GT）的发生和生长涉及到表面外胚层、内胚层和后肠内胚层的协调形成。GT的发育似乎反映了肢体的发育。尽管Shh对两个附属物的发育都是必不可少的，但它在GT发育中的作用远不如肢体中的作用清楚。在这里，通过在小鼠GT发育的不同阶段去除Shh，我们证明了Shh在GT起始和随后的雄激素非依赖性GT生长中是连续需要的。此外，我们通过组织特异性Cre系去除或激活其信号换能器Smo，研究了不同组织层的Hh反应性，并确定GT间质是Shh信号传导的主要靶组织。最后，我们发现Shh对于GT信号中心远端尿道上皮（dUE）的维持是必需的。通过遗传恢复Shh（-/-）阴囊内胚层中的Wnt-Fgf8信号，我们发现Shh部分通过dUE传递其信号，但独立于dUE信号调节Hoxa13和Hoxd13的表达。总之，我们提出Shh在GT发育中发挥核心作用，同时调节泄殖腔场的模式并支持生长信号。发展
Genital tubercle (GT) initiation and outgrowth involve coordinated morphogenesis of surface ectoderm, cloacal mesoderm and hindgut endoderm. GT development appears to mirror that of the limb. Although Shh is essential for the development of both appendages, its role in GT development is much less clear than in the limb. Here, by removing Shh at different stages during GT development in mice, we demonstrate a continuous requirement for Shh in GT initiation and subsequent androgen-independent GT growth. Moreover, we investigated the Hh responsiveness of different tissue layers by removing or activating its signal transducer Smo with tissue-specific Cre lines, and established GT mesenchyme as the primary target tissue of Shh signaling. Lastly, we showed that Shh is required for the maintenance of the GT signaling center distal urethral epithelium (dUE). By restoring Wnt-Fgf8 signaling in Shh(-/-) cloacal endoderm genetically, we revealed that Shh relays its signal partly through the dUE, but regulates Hoxa13 and Hoxd13 expression independently of dUE signaling. Altogether, we propose that Shh plays a central role in GT development by simultaneously regulating patterning of the cloacal field and supporting an outgrowth signal. DEVELOPMENT