Sonic hedgehog through Gli2 and Gli3 is required for the proper development of placental labyrinth.
Sonic hedgehog through Gli2 and Gli3 is required for the proper development of placental labyrinth.
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胎盘迷路的正常发育需要通过 Gli2 和 Gli3 的 Sonic Hedgehog
DOI：
10.1038/cddis.2015.28
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发表时间：
2015-02-19
影响因子：
9
通讯作者：
Wu XM
中科院分区：
文献类型：
--
作者：
Pan YB;Gong Y;Ruan HF;Pan LY;Wu XK;Tang C;Wang CJ;Zhu HB;Zhang ZM;Tang LF;Zou CC;Wang HB;Wu XM
Sonic hedgehog（Shh）是一种保守的形态发生蛋白，在从果蝇到人类的后生动物的各种器官的发育中发挥作用。在这里，我们研究了Shh信号在小鼠胎盘形成中的潜在作用和潜在机制。免疫组化显示Shh通路的主要成分在囊胚滋养外胚层和发育中的胎盘中都有丰富的表达。Shh的破坏导致卵黄囊血管生成受损，胎盘迷路分支减少和畸形，从而导致经胎盘通道能力的显著降低。此外，胎盘特异性基因掺入小鼠囊胚和囊胚移植的慢病毒转导强烈敲低Gli 3和Gli 2在胎盘中的表达，但不是在胚胎中。最后，Shh−/−胎盘中的Gli 3敲低部分挽救了卵黄囊和胎盘迷路的缺陷，并有力地恢复了经胎盘通道的能力。Shh+/-胎盘中Gli 2的敲除既不影响经胎盘通道的容量，也不影响卵黄囊的血管发生，但它部分地表现出Shh-/-胎盘的迷路缺陷。总之，这些结果揭示了Shh/Gli 2和Shh/Gli 3信号是小鼠胎盘正常发育所必需的，并且可能是妊娠维持所必需的。
Sonic hedgehog (Shh) functions as a conserved morphogen in the development of various organs in metazoans ranging from Drosophila to humans. Here, we have investigated the potential roles and underlying mechanisms of Shh signaling in murine placentation. Immunostaining revealed the abundant expression of the main components of Shh pathway in both the trophectoderm of blastocysts and developing placentas. Disruption of Shh led to impaired vascularogenesis of yolk sac, less branching and malformation of placental labyrinth, thereby leading to a robust decrease in capacity of transplacental passages. Moreover, placenta-specific gene incorporation by lentiviral transduction of mouse blastocysts and blastocyst transplantation robustly knocked down the expression of Gli3 and Gli2 in placenta but not in embryos. Finally, Gli3 knockdown in Shh−/− placentas partially rescued the defects of both yolk sac and placental labyrinth, and robustly restored the capacity of transplacental passages. Gli2 knockdown in Shh+/− placentas affected neither the capacity of tranplacental passages nor the vascularogenesis of yolk sac, however, it partially phenocopied the labyrinthine defects of Shh−/− placentas. Taken together, these results uncover that both Shh/Gli2 and Shh/Gli3 signals are required for proper development of murine placentas and are possibly essential for pregnant maintenance.