Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains.
The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ∼ 24 h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization.
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Joaquim
J
Grego-Bessa
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Jeffrey
J
Hildebrand
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA k-anderson@ski.mskcc.org.
Kathryn V
KV
Anderson
D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D016764:Cell Polarity; D048430:Cell Shape; D051338:Cofilin 1 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D054258:Neural Plate / Q000166:cytology / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D054259:Neural Tube / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010766:Phosphorylation; D062725:Tight Junction Proteins / Q000378:metabolism; D000099149:Ezrin
D000199:Actins; D000205:Actomyosin; D015415:Biomarkers; D051338:Cofilin 1; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D062725:Tight Junction Proteins; D000099149:Ezrin; C402112:Shrm protein, mouse; C071058:moesin; C071776:radixin
Actin; Cofilin; Epithelial polarity; Mouse genetics; Neural tube; SHROOM3