MID1 and MID2 are required for Xenopus neural tube closure through the regulation of microtubule organization
MID1 and MID2 are required for Xenopus neural tube closure through the regulation of microtubule organization
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DOI：
10.1242/dev.048769
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发表时间：
2010-07-15
期刊：
影响因子：
4.6
通讯作者：
Ueno, Naoto
中科院分区：
文献类型：
--
作者：
Suzuki, Makoto;Hara, Yusuke;Ueno, Naoto
神经管的关闭既需要改变细胞形状，也需要保持细胞形状。这种变化主要通过两个协调的形态发生事件发生：细胞伸长和顶端收缩。包括微管在内的细胞骨架元素在体内如何调控这一过程在很大程度上是未知的。在这里，我们表明非洲爪哇的神经管关闭依赖于两个蛋白质的同源基因：MID1，它与人类的Opitz G/BBB综合征有关，以及它的Paralog MID2。由吗啉介导的敲除非洲爪蛙MIDs(XMIDs)破坏了神经板上皮的形态，导致神经管缺陷。在xMID耗尽的神经板中，正常的上皮组织受到干扰，但不影响神经的命运。此外，xMID基因敲除破坏了微管的稳定性，并导致微管的解体，微管通常是根尖基极化的，这是导致异常表型的原因。我们还发现，在神经板重建过程中，xMIDs及其相互作用蛋白Mig12是微管稳定所必需的。最后，我们证明了xMID是形成多个上皮器官所必需的。我们认为，类似的中间调控机制是上皮组织和器官正常形态发生的基础，包括Opitz G/BBB综合征患者受影响的组织。
Closure of the neural tube requires both the change and maintenance of cell shape. The change occurs mainly through two coordinated morphogenetic events: cell elongation and apical constriction. How cytoskeletal elements, including microtubules, are regulated in this process in vivo is largely unknown. Here, we show that neural tube closure in Xenopus depends on orthologs of two proteins: MID1, which is responsible for Opitz G/BBB syndrome in humans, and its paralog MID2. Depletion of the Xenopus MIDs (xMIDs) by morpholino-mediated knockdown disrupted epithelial morphology in the neural plate, leading to neural tube defects. In the xMID-depleted neural plate, the normal epithelial organization was perturbed without affecting neural fate. Furthermore, the xMID knockdown destabilized and caused the disorganization of microtubules, which are normally apicobasally polarized, accounting for the abnormal phenotypes. We also found that the xMIDs and their interacting protein Mig12 were coordinately required for microtubule stabilization during remodeling of the neural plate. Finally, we showed that the xMIDs are required for the formation of multiple epithelial organs. We propose that similar MID-governed mechanisms underlie the normal morphogenesis of epithelial tissues and organs, including the tissues affected in patients with Opitz G/BBB syndrome.