mig-38, a novel gene that regulates distal tip cell turning during gonadogenesis in C. elegans hermaphrodites
mig-38, a novel gene that regulates distal tip cell turning during gonadogenesis in C. elegans hermaphrodites
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DOI：
10.1016/j.ydbio.2012.06.011
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发表时间：
2012-08-15
影响因子：
2.7
通讯作者：
Schwarzbauer, Jean E.
中科院分区：
文献类型：
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作者：
Martynovsky, Maria;Wong, Ming-Ching;Schwarzbauer, Jean E.
在秀丽隐杆线虫的性腺形态发生中，两个两性性腺臂的最终U型是由远端顶端细胞(DTC)的迁移决定的。这些体细胞在腹侧基底膜上以相反的方向迁移，直到特定的细胞外线索诱导从腹侧转向背侧，然后向心地朝向背侧基底膜的中体区。为了探讨DTC翻转的机制，我们研究了一个新基因F40F11.2/MiG-38的作用，该基因被RNAi耗尽，导致DTC翻转失败，从而使DTC继续迁移离开中体区。MiG-38在性腺原基中表达，并在DTC迁移过程中持续表达，在此过程中它以细胞自主的方式控制DTC的转向。编码整合素黏附受体的mig-38和ina-1的RNAi缺失增加了转向表型的丢失，表明这些基因之间存在遗传相互作用。此外，整合素相关蛋白MIG-15/NCK相互作用蛋白(NIK)与MIG-38共同作用，引导DTC转向，如MiG-38与MiG-15(Rh80)低晶型的RNAi所示。这些结果表明，MIG-38增强了MIG-15在整合素依赖的DTC转向中的作用。Talin是一种对整合素激活至关重要的蛋白质，它的敲除会导致DTCs过早停止迁移。当TALIN和MIG-38都被RNAi处理耗尽时，过早停止的表型被抑制。当MIG-15或其结合伙伴NCK-1进一步耗尽时，这种抑制作用被逆转。这些结果表明，Talin和MIG-15/NCK-1复合体都能促进DTC运动，MIG-38可能是该复合体的负性调节因子。我们提出了一个模型来解释MIG-38在运动和转身中的双重作用。(C)2012 Elsevier Inc.保留所有权利。
In Caenorhabditis elegans gonad morphogenesis, the final U-shapes of the two hermaphrodite gonad arms are determined by migration of the distal tip cells (DTCs). These somatic cells migrate in opposite directions on the ventral basement membrane until specific extracellular cues induce turning from ventral to dorsal and then centripetally toward the midbody region on the dorsal basement membrane. To dissect the mechanism of DTC turning, we examined the role of a novel gene, F40F11.2/mig-38, whose depletion by RNAi results in failure of DTC turning so that DTCs continue their migration away from the midbody region. mig-38 is expressed in the gonad primordium, and expression continues throughout DTC migration where it acts cell-autonomously to control DTC turning. RNAi depletion of both mig-38 and ina-1, which encodes an integrin adhesion receptor, enhanced the loss of turning phenotype indicating a genetic interaction between these genes. Furthermore, the integrin-associated protein MIG-15/Nck-interacting kinase (NIK) works with MIG-38 to direct DTC turning as shown by mig-38 RNAi with the mig-15(rh80) hypomorph. These results indicate that MIG-38 enhances the role of MIG-15 in integrin-dependent DTC turning. Knockdown of talin, a protein that is important for integrin activation, causes the DTCs to stop migration prematurely. When both talin and MIG-38 were depleted by RNAi treatment, the premature stop phenotype was suppressed. This suppression effect was reversed upon additional depletion of MIG-15 or its binding partner NCK-1. These results suggest that both talin and the MIG-15/NCK-1 complex promote DTC motility and that MIG-38 may act as a negative regulator of the complex. We propose a model to explain the dual role of MIG-38 in motility and turning. (C) 2012 Elsevier Inc. All rights reserved.