The actin depolymerizing factor n-cofilin is essential for neural tube morphogenesis and neural crest cell migration

被引:178
作者
Gurniak, CB [1 ]
Perlas, E [1 ]
Witke, W [1 ]
机构
[1] European Mol Biol Lab, Mouse Biol Programme, I-00016 Monterotondo, Italy
关键词
cofilin; actin depolymerizing factor; neural crest cell migration; actin cytoskeleton;
D O I
10.1016/j.ydbio.2004.11.010
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cofilin/ADF proteins are a ubiquitously expressed family of F-actin depolymerizing factors found in eukaryotic cells including plants. In vitro, cofilin/ADF activity has been shown to be essential for actin driven motility, by accelerating actin filament turnover. Three actin depolyinerizing factors (n-cofilin, m-cofilin, ADF) can be found in mouse and human. Here we show that in mouse the non-muscle-specific gene-n-cofilin-is essential for migration of neural crest cells as well as other cell types in the paraxial mesoderm. The main defects observed in n-cofilin mutant embryos are an impaired delamination and migration of neural crest cells, affecting the development of neural crest derived tissues. Neural crest cells lacking n-cofilin do not polarize, and F-actin bundles or fibers are not detectable. In addition, n-cofilin is required for neuronal precursor cell proliferation and scattering. These defects result in a complete lack of neural tube closure in n-cofilin mutant embryos. Although ADF is overexpressed in mutant embryos, this cannot compensate the lack of n-cofilin, suggesting. that they might have a different function in embryonic development. Our data suggest that in mammalian development, regulation of the actin cytoskeleton by the F-actin depolymerizing factor n-cofilin is critical for epithelial-mesencbymal type of cell shape changes as well as cell proliferation. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:231 / 241
页数:11
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