Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity.

Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity.
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DOI:
10.1083/jcb.200602062
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发表时间:
2006-07-17
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Gumbiner BM
Gumbiner BM
中科院分区:
其他
文献类型:
--
作者:
Chen X;Gumbiner BM

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关于原钙粘蛋白在细胞粘附和组织发育中的作用知之甚少。旁轴原钙粘蛋白(PAPC)控制非洲爪蟾胚胎的细胞分选和形态发生运动。我们发现PAPC通过下调C-cadherin的粘附活性来调节这些功能。外源性c -钙粘蛋白的表达可逆转papc诱导的细胞分选和原肠胚形成缺陷。此外,内源性PAPC的缺失导致中胚层背侧C-cadherin粘附活性升高,干扰正常的囊胚闭合,这一缺陷可以通过显性阴性的C-cadherin突变体来修复。重要的是,激活素诱导了PAPC的表达,而PAPC是激活素诱导的C-cadherin粘附活性和外植体形态发生的调控所必需的。PAPC对C-cadherin的调控不需要通过frizzled7信号传导,这表明C-cadherin调控和frizzled7信号传导是PAPC途径中诱导形态发生运动的两个不同分支。因此,原钙粘蛋白的局部表达对经典钙粘蛋白粘附功能的空间调控是一种控制细胞分选和组织形态发生的新机制。
Little is known about how protocadherins function in cell adhesion and tissue development. Paraxial protocadherin (PAPC) controls cell sorting and morphogenetic movements in the Xenopus laevis embryo. We find that PAPC mediates these functions by down-regulating the adhesion activity of C-cadherin. Expression of exogenous C-cadherin reverses PAPC-induced cell sorting and gastrulation defects. Moreover, loss of endogenous PAPC results in elevated C-cadherin adhesion activity in the dorsal mesoderm and interferes with the normal blastopore closure, a defect that can be rescued by a dominant-negative C-cadherin mutant. Importantly, activin induces PAPC expression, and PAPC is required for activin-induced regulation of C-cadherin adhesion activity and explant morphogenesis. Signaling through Frizzled-7 is not required for PAPC regulation of C-cadherin, suggesting that C-cadherin regulation and Frizzled-7 signaling are two distinct branches of the PAPC pathway that induce morphogenetic movements. Thus, spatial regulation of classical cadherin adhesive function by local expression of a protocadherin is a novel mechanism for controlling cell sorting and tissue morphogenesis.
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