The actin depolymerizing factor n-cofilin is essential for neural tube morphogenesis and neural crest cell migration.
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.
Gurniak
Christine B
CB
European Molecular Biology Laboratory, Mouse Biology Programme, Adriano Buzzati-Traverso Campus, via Ramarini 32, 00016 Monterotondo, Italy.
Perlas
Emerald
E
Witke
Walter
W
D051339:Actin Depolymerizing Factors; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D051340:Cofilin 2; D051345:Destrin; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005804:Genes, Lethal; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009436:Neural Tube Defects / Q000196:embryology / Q000209:etiology / Q000235:genetics
D051339:Actin Depolymerizing Factors; C495816:Cfl2 protein, mouse; D051340:Cofilin 2; D051345:Destrin; C495825:Dstn protein, mouse; D008840:Microfilament Proteins