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 cau ses exencephaly, acrania, facial clefting, and spina bifida, all of which c an be attributed to failed neural tube closure. This mutation is designated shroom (shrm) because the neural folds "mushroom" outward and do not conve rge at the dorsal midline. shrm encodes a PDZ domain protein that is involv ed at several levels in regulating aspects of cytoarchitecture. First, endo genous Shrm localizes to adherens junctions and the cytoskeleton. Second, e ctopically expressed Shrm alters the subcellular distribution of F-actin. T hird, Shrm directly binds F-actin. Finally, cytoskeletal polarity within th e neuroepithelium is perturbed in mutant embryos. In concert, these observa tions suggest that Shrm is a critical determinant of the cellular architect ure required for proper neurulation.