Neural defects caused by total and Wnt1-Cre mediated ablation of p120ctn in mice

BMC Developmental Biology

article

Pieters, Tim¹  Sanders, Ellen¹  Tian, Huiyu¹  van Hengel, Jolanda¹  van Roy, Frans¹ 

[1] Molecular Cell Biology Unit, Center for Inflammation Research;Department of Biomedical Molecular Biology, Ghent University;Present address: Faculty of Medicine and Health Sciences, Ghent University Hospital;Present address: Ministry of Education, College of Life Sciences, Shandong University

关键词: p120 catenin;    Knockout mouse;    Wnt1;    NTD;    Exencephaly;    Neural fold closure;    Cadherins;    Actin binding proteins;   

DOI  :  10.1186/s12861-020-00222-4

学科分类：生物科学（综合）

来源: BioMed Central

【 摘 要 】

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.

【 授权许可】

CC BY