Scribble mutation disrupts convergent extension and apical constriction during mammalian neural tube closure

Morphogenesis of the neural tube in vertebrates relies on elongation and bending of the neural plate epithelium, which is driven at the cellular level by polarized cell intercalation, cell shape changes, and the underlying cytoskeletal dynamics that promotes these behaviors. Mutations of the gene encoding Scribble (Scrib) lead to neural tube defects in mice, however the cellular and molecular mechanisms by which Scribble regulates neural cell behavior remain unknown. Our analysis of neural development in Scribble mutants characterizes several defects in overall tissue shape changes. Live cell imaging of mouse embryos revealed that the Scrib mutation leads to defects in polarized cell intercalation and rosette resolution, as well as loss of apical constriction and cell wedging. Scrib mutant embryos displayed aberrant localization and expression of the junctional proteins ZO-1, Par3, Par6, aPKC, and cadherins, as well as the cytoskeletal proteins actin and myosin. These findings identify a novel role for Scrib in regulating neural cell behavior during NTC and further our understanding of the molecular mechanisms involved in mammalian neural development.