Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice.
Using gene trap mutagenesis, we have identified a mutation in mice that causes exencephaly, acrania, facial clefting, and spina bifida, all of which can be attributed to failed neural tube closure. This mutation is designated shroom (shrm) because the neural folds "mushroom" outward and do not converge at the dorsal midline. shrm encodes a PDZ domain protein that is involved at several levels in regulating aspects of cytoarchitecture. First, endogenous Shrm localizes to adherens junctions and the cytoskeleton. Second, ectopically expressed Shrm alters the subcellular distribution of F-actin. Third, Shrm directly binds F-actin. Finally, cytoskeletal polarity within the neuroepithelium is perturbed in mutant embryos. In concert, these observations suggest that Shrm is a critical determinant of the cellular architecture required for proper neurulation.
Hildebrand
J D
JD
Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Soriano
P
P
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002451:Cell Compartmentation; D016764:Cell Polarity / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology*; D003599:Cytoskeleton / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D017930:Genes, Reporter; D007365:Intercellular Junctions; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D009436:Neural Tube Defects / Q000235:genetics*; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D000199:Actins; D008840:Microfilament Proteins; C402112:Shrm protein, mouse