p120 catenin (p120ctn) is an important component in the cadherin-catenin cell adhesion complex because it stabilizes cadherin-mediated intercellular junctions. Outside these junctions, p120ctn is actively involved in the regulation of small GTPases of the Rho family, in actomyosin dynamics and in transcription regulation. We and others reported that loss of p120ctn in mouse embryos results in an embryonic lethal phenotype, but the exact developmental role of p120ctn during brain formation has not been reported. We combined floxed p120ctn mice with Del-Cre or Wnt1-Cre mice to deplete p120ctn from either all cells or specific brain and neural crest cells. Complete loss of p120ctn in mid-gestation embryos resulted in an aberrant morphology, including growth retardation, failure to switch from lordotic to fetal posture, and defective neural tube formation and neurogenesis. By expressing a wild-type p120ctn from the ROSA26 locus in p120ctn-null mouse embryonic stem cells, we could partially rescue neurogenesis. To further investigate the developmental role of p120ctn in neural tube formation, we generated conditional p120ctnfl/fl;Wnt1Cre knockout mice. p120ctn deletion in Wnt1-expressing cells resulted in neural tube closure defects (NTDs) and craniofacial abnormalities. These defects could not be correlated with misregulation of brain marker genes or cell proliferation. In contrast, we found that p120ctn is required for proper expression of the cell adhesion components N-cadherin, E-cadherin and β-catenin, and of actin-binding proteins cortactin and Shroom3 at the apical side of neural folds. This region is of critical importance for closure of neural folds. Surprisingly, the lateral side of mutant neural folds showed loss of p120ctn, but not of N-cadherin, β-catenin or cortactin. These results indicate that p120ctn is required for neurogenesis and neurulation. Elimination of p120ctn in cells expressing Wnt1 affects neural tube closure by hampering correct formation of specific adhesion and actomyosin complexes at the apical side of neural folds. Collectively, our results demonstrate the crucial role of p120ctn during brain morphogenesis.

中文翻译：

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由小鼠的W120和Wnt1-Cre介导的p120ctn消融引起的神经缺陷。

p120 catenin（p120ctn）是钙粘蛋白-catenin细胞粘附复合物的重要组成部分，因为它可以稳定钙粘蛋白介导的细胞间连接。在这些连接以外，p120ctn积极参与了Rho家族小GTPases的调控，肌动球蛋白动力学和转录调控。我们和其他人报告说，小鼠胚胎中p120ctn的缺失会导致胚胎致死表型，但尚未报道p120ctn在大脑形成过程中的确切发育作用。我们将疏散的p120ctn小鼠与Del-Cre或Wnt1-Cre小鼠结合，以从所有细胞或特定的脑和神经rest细胞中消耗p120ctn。妊娠中期胚胎中p120ctn的完全丧失导致异常形态，包括生长迟缓，无法从脊柱前凸转为胎儿姿势，和有缺陷的神经管形成和神经发生。通过在p120ctn-null小鼠胚胎干细胞中从ROSA26基因座表达野生型p120ctn，我们可以部分挽救神经发生。为了进一步研究p120ctn在神经管形成中的发育作用，我们产生了条件性p120ctnfl / fl; Wnt1Cre基因敲除小鼠。Wnt1表达细胞中的p120ctn缺失导致神经管闭合缺陷（NTD）和颅面异常。这些缺陷可能与脑标志物基因的失调或细胞增殖无关。相反，我们发现p120ctn是细胞粘附成分N-钙粘蛋白，E-钙粘蛋白和β-连环蛋白以及肌动蛋白结合蛋白cortactin和Shroom3在神经折叠顶端的正确表达所必需的。该区域对于神经折叠的闭合至关重要。出人意料的是，突变神经折叠的外侧显示出p120ctn的损失，但没有N-钙粘着蛋白，β-连环蛋白或cortactin的损失。这些结果表明，p120ctn是神经发生和神经形成所必需的。消除表达Wnt1的细胞中的p120ctn会通过阻碍神经折叠顶端的特异性黏附和肌动球蛋白复合物的正确形成而影响神经管的闭合。总的来说，我们的结果证明了p120ctn在脑形态发生过程中的关键作用。消除表达Wnt1的细胞中的p120ctn会通过阻碍神经折叠顶端的特异性黏附和肌动球蛋白复合物的正确形成而影响神经管的闭合。总的来说，我们的结果证明了p120ctn在脑形态发生过程中的关键作用。消除表达Wnt1的细胞中的p120ctn会通过阻碍神经折叠顶端的特异性黏附和肌动球蛋白复合物的正确形成而影响神经管的闭合。总的来说，我们的结果证明了p120ctn在脑形态发生过程中的关键作用。