TY - JOUR
T1 - Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice
AU - Hildebrand, Jeffrey D.
AU - Soriano, Philippe
N1 - Funding Information:
With the discovery that Shrm is a PDZ domain–containing actin-binding protein that colocalizes with F-actin and AJs, it is tempting to speculate that the NTDs we observe are directly related to aberrant cytoskeletal architecture, cell polarity, or cell adhesion. Our results support this hypothesis, since the integrity of the apical cytoskeleton is perturbed in the neuroepithelium of shrm mutant embryos. It is currently unclear where Shrm sits in the pathway leading from cadherin-mediated adhesion to cytoskeletal organization. It is possible that Shrm acts at the level of AJ formation. This idea is partially supported by the observation that β-catenin is somewhat mislocalized in shrm mutant embryos. However, because Shrm-deficient primary neural tube cells form vinculin- and β-catenin-positive AJs in vitro, we cannot rule out the possibility that the observed perturbation in β-catenin localization is secondary to a cytoskeletal defect. Alternatively, it is possible that Shrm binds actin and helps to localize or stabilize the cortical cytoskeleton. Both of these possibilities are supported by the mislocalization of F-actin and cortactin in shrm mutants.
PY - 1999/11/24
Y1 - 1999/11/24
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0033601076
U2 - 10.1016/S0092-8674(00)81537-8
DO - 10.1016/S0092-8674(00)81537-8
M3 - Article
C2 - 10589677
AN - SCOPUS:0033601076
SN - 0092-8674
VL - 99
SP - 485
EP - 497
JO - Cell
JF - Cell
IS - 5
ER -