TY - JOUR T1 - <em>Scribble</em> mutation disrupts convergent extension and apical constriction during mammalian neural tube closure JF - bioRxiv DO - 10.1101/2020.09.18.303446 SP - 2020.09.18.303446 AU - Alyssa C. Lesko AU - Raymond Keller AU - Ping Chen AU - Ann Sutherland Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/25/2020.09.18.303446.abstract N2 - Morphogenesis of the vertebrate neural tube occurs by elongation and bending of the neural plate, tissue shape changes that are driven at the cellular level by polarized cell intercalation and cell shape changes, notably apical constriction and cell wedging. Coordinated cell intercalation, apical constriction, and wedging undoubtedly require complex underlying cytoskeletal dynamics and remodeling of adhesions. Mutations of the gene encoding Scribble result in neural tube defects in mice, however the cellular and molecular mechanisms by which Scrib regulates neural cell behavior remain unknown. Analysis of Scribble mutants revealed defects in neural tissue shape changes, and live cell imaging of mouse embryos showed that the Scrib mutation results in defects in polarized cell intercalation, particularly in rosette resolution, and failure of both cell apical constriction and cell wedging. Scrib mutant embryos displayed aberrant expression of the junctional proteins ZO-1, Par3, Par6, E- and N-cadherins, and the cytoskeletal proteins actin and myosin. These findings show that Scribble has a central role in organizing the molecular complexes regulating the morphomechanical neural cell behaviors underlying vertebrate neurulation, and they advance our understanding of the molecular mechanisms involved in mammalian neural tube closure.HighlightsPolarized cell intercalation is lost in Scrib mutant embryosScrib mutation has specific effects on rosette formation and resolutionScrib mutation disrupts apical constriction and cell shape changes necessary for neural tube closureAdherens and tight junction composition is altered in the neural epithelial cells of Scrib mutantsCompeting Interest StatementThe authors have declared no competing interest. ER -