Mech Dev. 2018 Feb;149:41-52. doi: 10.1016/j.mod.2018.01.002. Epub 2018 Jan 31.
In vertebrates, the neural crest is a unique population of pluripotent cells whose development is dependent on signaling from neighboring tissues. Cadherin family members, including protocadherins, are emerging as major players in neural crest development, largely through their roles in cell adhesion and sorting in embryonic tissues. Here, we show that Protocadherin 7 (Pcdh7), previously shown to function in sensorial layer integrity and neural tube closure in Xenopus, is also involved in neural crest specification and survival. Pcdh7 expression partly overlaps the neural crest domain at the lateral neural crest border. Pcdh7 knockdown in embryos does not alter neural crest induction; however, neural crest specification markers, including Snail2 and Sox9, are lost, due to apoptosis of the neural crest starting after stage 13. Pcdh7 knockdown also results in downregulation of Wnt11b; both of which are co-expressed in the sensorial layer lateral to the neural crest, suggestive of a role for Wnt11b in the neural crest apoptosis. Confirming this role, apoptosis, Snail2 expression and the developmental fate of the neural crest can be partially rescued by ectopic expression of Wnt11b. These results indicate that Pcdh7 plays an important role in maintaining the sensorial layer at the lateral neural crest border, which is necessary for the secretion of survival factors, including Wnt11b.
在脊椎动物中，神经嵴是一种独特的多能细胞群体，其发育依赖于来自邻近组织的信号。钙粘蛋白家族成员，包括原钙粘蛋白，作为神经嵴发育的主要参与者而出现，主要通过其在胚胎组织中的细胞黏附和分选作用。在这里，我们表明原钙粘蛋白 7（Pcdh7）在 Xenopus 中先前被证明在感觉层完整性和神经管闭合中起作用，也参与神经嵴的特化和存活。Pcdh7 的表达与神经嵴边界的侧神经嵴域部分重叠。胚胎中的 Pcdh7 敲低不会改变神经嵴的诱导；然而，神经嵴特化标志物，包括 Snail2 和 Sox9，由于神经嵴的凋亡而丢失，起始于 13 期之后。Pcdh7 敲低也导致 Wnt11b 的下调；两者均在神经嵴侧面的感觉层中共同表达，提示 Wnt11b 在神经嵴凋亡中起作用。证实了这一作用，通过异位表达 Wnt11b，可以部分挽救凋亡、Snail2 表达和神经嵴的发育命运。这些结果表明，Pcdh7 在维持神经嵴侧部感觉层中起着重要作用，这对于包括 Wnt11b 在内的存活因子的分泌是必要的。
