期刊
DEVELOPMENTAL BIOLOGY
卷 478, 期 -, 页码 59-75出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2021.05.013
关键词
Convergent extension; Apical constriction; Neural tube closure; Scribble; Planar cell polarity; Cell intercalation
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human [Development-R01HD087093]
Formation of the vertebrate neural tube involves cell level processes such as polarized cell intercalation and shape changes, which are driven by gene expression and cytoskeletal dynamics. Mutations in the Scribble gene have been linked to neural tube defects in mice, affecting cell behavior at the molecular level. This study shows that Scribble plays a central role in regulating the molecular complexes and morphomechanical behaviors underlying neural tube formation in mammals.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据