Differential Expression of a Classic Cadherin Directs Tissue-Level Contractile Asymmetry during Neural Tube Closure
Differential Expression of a Classic Cadherin Directs Tissue-Level Contractile Asymmetry during Neural Tube Closure
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DOI：
10.1016/j.devcel.2019.10.001
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发表时间：
2019-10-21
影响因子：
11.8
通讯作者：
Munro, Edwin
中科院分区：
文献类型：
--
作者：
Hashimoto, Hidehiko;Munro, Edwin
胚胎在组织边界控制力的产生，但它们是如何做到这一点的仍然知之甚少。在这里，我们展示了如何组织特异性表达的II型钙粘蛋白，钙粘蛋白2，图案肌动球蛋白收缩沿着组织边界控制拉链和神经管关闭在基底脊索动物，玻璃海鞘。钙粘蛋白2在沿着神经/表皮（Ne/Epi）边界的神经细胞中差异表达和同型富集，其中RhoA和肌球蛋白在拉链进展期间被激活。同型富集的钙粘蛋白2将Rho GTP酶激活蛋白Gap 21/23隔离到同型连接处。Gap 21/23进而将RhoA/肌球蛋白活性重定向至异型Ne/Epi连接处。通过激活肌球蛋白II沿着拉链前面的Ne/Epi连接点，并抑制肌球蛋白II沿着拉链后面新形成的Ne/Ne连接点，钙粘蛋白2促进组织水平的收缩不对称性，以驱动拉链的进展。我们提出，在许多其他情况下，连接交换的动态耦合局部收缩性的变化可能会控制上皮细胞的融合和分离。
Embryos control force generation at tissue boundaries, but how they do so remains poorly understood. Here we show how tissue-specific expression of the type II cadherin, Cadherin2, patterns actomyosin contractility along tissue boundaries to control zippering and neural tube closure in the basal chordate, Ciona robusta. Cadherin2 is differentially expressed and homotypically enriched in neural cells along the neural/epidermal (Ne/Epi) boundary, where RhoA and myosin are activated during zipper progression. Homotypically enriched Cadherin2 sequesters the Rho GTPase-activating protein, Gap21/23, to homotypic junctions. Gap21/23 in turn redirects RhoA/myosin activity to heterotypic Ne/Epi junctions. By activating myosin II along Ne/Epi junctions ahead of the zipper and inhibiting myosin II along newly formed Ne/Ne junctions behind the zipper, Cadherin2 promotes tissue-level contractile asymmetry to drive zipper progression. We propose that dynamic coupling of junction exchange to local changes in contractility may control fusion and separation of epithelia in many other contexts.