Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains
Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains
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DOI：
10.1242/dev.115493
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发表时间：
2015-04-01
期刊：
影响因子：
4.6
通讯作者：
Anderson, Kathryn V.
中科院分区：
文献类型：
--
作者：
Grego-Bessa, Joaquim;Hildebrand, Jeffrey;Anderson, Kathryn V.
哺乳动物上皮细胞极性和动力学的遗传控制可以在小鼠神经管形态发生过程中以细胞分辨率在体内研究。小鼠神经板是单层上皮，在大约24 h的过程中转化为柱状假复层管。已知顶端F-肌动蛋白对于神经管闭合是重要的，但是肌动蛋白动力学在神经上皮中的确切作用尚不清楚。要确定如何组织的神经上皮细胞和神经管关闭时，肌动蛋白动力学的影响，我们研究了小鼠突变体，缺乏肌动蛋白切割蛋白cofilin 1（CFL 1）的神经管关闭缺陷的细胞基础。虽然在突变体中，粘附连接、Par复合体、Crumbs复合体和SHROOM 3的顶端定位是正常的，但CFL 1在神经板的顶端和基底域中具有至少两种不同的功能。在顶端，在没有CFL 1的情况下，肌球蛋白轻链不会磷酸化，表明CFL 1是激活神经管闭合所需的顶端肌动球蛋白所必需的。在神经板的基底侧，CFL 1的缺失对肌球蛋白有相反的影响：过量的F-肌动蛋白和肌球蛋白积累，异位肌球蛋白轻链被磷酸化。F-肌动蛋白的基底积累与异位基底紧密连接的组装和基底膜的局灶性破坏相关，这最终导致上皮组织的破坏。
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 similar to 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.