TRPM7 regulates gastrulation during vertebrate embryogenesis
TRPM7 regulates gastrulation during vertebrate embryogenesis
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DOI：
10.1016/j.ydbio.2010.11.034
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发表时间：
2011-02-15
影响因子：
2.7
通讯作者：
Runnels, Loren W.
中科院分区：
文献类型：
--
作者：
Liu, Wei;Su, Li-Ting;Runnels, Loren W.
在原肠胚形成期间。背缘区的细胞伸展、伸长、排列和插入以建立发育中的胚胎的身体轴。在这里，我们证明了双功能通道激酶TRPM 7是脊椎动物原肠胚形成所必需的。TRPM 7在母体和整个发育过程中暂时表达，并且在原肠胚形成期间经历会聚延伸的组织中空间富集。功能研究表明，TRPM 7的离子通道，但不是它的激酶结构域，具体影响细胞极性和收敛的延伸运动原肠胚形成过程中，独立的中胚层规格。在原肠胚形成期间。通过Dishevelled（DvI）的非经典Wnt途径协调GTP酶Rho和Rat的活性以控制会聚性伸展运动。我们发现TRPM 7与非经典Wnt信号传导协同作用以调节大鼠活动。由Ca 2 +-和Mg 2 +-渗透TRPM 7的耗竭引起的表型被显性负性形式的Rac的表达以及Mg 2+补充或Mg 2+转运蛋白SLC 41 A2的表达抑制。一起这些研究证实了离子通道TRPM 7和Mg 2+在脊椎动物原肠胚形成期间的Rac依赖性极化细胞运动中的重要作用。(C)2010年爱思唯尔公司All rights reserved.
During gastrulation. cells in the dorsal marginal zone polarize, elongate, align and intercalate to establish the physical body axis of the developing embryo. Here we demonstrate that the bifunctional channel-kinase TRPM7 is specifically required for vertebrate gastrulation. TRPM7 is temporally expressed maternally and throughout development, and is spatially enriched in tissues undergoing convergent extension during gastrulation. Functional studies reveal that TRPM7's ion channel, but not its kinase domain, specifically affects cell polarity and convergent extension movements during gastrulation, independent of mesodermal specification. During gastrulation. the non-canonical Wnt pathway via Dishevelled (DvI) orchestrates the activities of the GTPases Rho and Rat to control convergent extension movements. We find that TRPM7 functions synergistically with non-canonical Wnt signaling to regulate Rat activity. The phenotype caused by depletion of the Ca2+- and Mg2+-permeant TRPM7 is suppressed by expression of a dominant negative form of Rac, as well as by Mg2+ supplementation or by expression of the Mg2+ transporter SLC41A2. Together. these studies demonstrate an essential role for the ion channel TRPM7 and Mg2+ in Rac-dependent polarized cell movements during vertebrate gastrulation. (C) 2010 Elsevier Inc. All rights reserved.