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

• Published in: Developmental biology Vol. 278; no. 1; pp. 231 - 241
• Main Authors: Gurniak, Christine B., Perlas, Emerald, Witke, Walter
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2005
• Subjects: Actin cytoskeleton; Actin depolymerizing factor; Actin Depolymerizing Factors; Animals; Cell Movement - genetics; Cell Movement - physiology; Cofilin; Cofilin 2; Destrin; Gene Expression Regulation, Developmental; Gene Targeting; Genes, Lethal; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Knockout; Microfilament Proteins - deficiency; Microfilament Proteins - genetics; Microfilament Proteins - physiology; Morphogenesis - genetics; Morphogenesis - physiology; Nervous System - cytology; Nervous System - embryology; Nervous System - metabolism; Neural Crest - cytology; Neural Crest - embryology; Neural Crest - metabolism; Neural crest cell migration; Neural Tube Defects - embryology; Neural Tube Defects - etiology; Neural Tube Defects - genetics; Neural crest cell migration; Cofilin; Actin depolymerizing factor; Actin cytoskeleton
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2004.11.010

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 depolymerizing 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–mesenchymal type of cell shape changes as well as cell proliferation.