Scribble mutation disrupts convergent extension and apical constriction during mammalian neural tube closure.
Scribble mutation disrupts convergent extension and apical constriction during mammalian neural tube closure.
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DOI：
10.1016/j.ydbio.2021.05.013
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发表时间：
2021-10
影响因子：
2.7
通讯作者：
Sutherland A
中科院分区：
文献类型：
--
作者：
Lesko AC;Keller R;Chen P;Sutherland A
脊椎动物神经管的形态发生是通过神经板的伸长和弯曲、极化细胞嵌入和细胞形状变化（特别是顶端收缩和细胞楔入）在细胞水平驱动的组织形状变化而发生的。协调的细胞嵌入、顶端收缩和楔入无疑需要复杂的基础细胞骨架动力学和粘附重塑。编码 Scribble 的基因突变会导致小鼠神经管缺陷，但 Scrib 调节神经细胞行为的细胞和分子机制仍不清楚。对 Scribble 突变体的分析揭示了神经组织形状变化的缺陷，小鼠胚胎的活细胞成像表明 Scribble 突变导致极化细胞嵌入缺陷，特别是玫瑰花结分辨率，以及细胞顶端收缩和细胞楔入的失败。 Scrib突变胚胎表现出连接蛋白ZO-1、Par3、Par6、E-和N-钙粘蛋白以及细胞骨架蛋白肌动蛋白和肌球蛋白的异常表达。这些发现表明，Scribble 在组织调节脊椎动物神经形成的形态力学神经细胞行为的分子复合物方面发挥着核心作用，并且它们增进了我们对哺乳动物神经管闭合所涉及的分子机制的理解。
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.
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DOI：
10.1073/pnas.1700934114
发表时间：
2017-06-27
影响因子：
11.1
作者：
Galea, Gabriel L.;Cho, Young-June;Copp, Andrew J.
通讯作者：
Copp, Andrew J.
影响因子：
2.7
作者：
FRISTROM, D
通讯作者：
FRISTROM, D
影响因子：
4
作者：
Escuin S;Vernay B;Savery D;Gurniak CB;Witke W;Greene ND;Copp AJ
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Copp AJ
影响因子：
21.3
作者：
Collinet, Claudio;Rauzi, Matteo;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
影响因子：
11.8
作者：
Chien YH;Srinivasan S;Keller R;Kintner C
通讯作者：
Kintner C