Lin Fang, Sepich Diane S, Chen Songhai, Topczewski Jacek, Yin Chunyue, Solnica-Krezel Lilianna, Hamm Heidi
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
J Cell Biol. 2005 Jun 6;169(5):777-87. doi: 10.1083/jcb.200501104. Epub 2005 May 31.
Galpha(12/13) have been implicated in numerous cellular processes, however, their roles in vertebrate gastrulation are largely unknown. Here, we show that during zebrafish gastrulation, suppression of both Galpha(12) and Galpha(13) signaling by overexpressing dominant negative proteins and application of antisense morpholino-modified oligonucleotide translation interference disrupted convergence and extension without changing embryonic patterning. Analyses of mesodermal cell behaviors revealed that Galpha(12/13) are required for cell elongation and efficient dorsalward migration during convergence independent of noncanonical Wnt signaling. Furthermore, Galpha(12/13) function cell-autonomously to mediate mediolateral cell elongation underlying intercalation during notochord extension, likely acting in parallel to noncanonical Wnt signaling. These findings provide the first evidence that Galpha(12) and Galpha(13) have overlapping and essential roles in distinct cell behaviors that drive vertebrate gastrulation.
Gα（12/13）已被证明参与多种细胞过程，然而，它们在脊椎动物原肠胚形成中的作用在很大程度上尚不清楚。在这里，我们表明，在斑马鱼原肠胚形成过程中，通过过表达显性负性蛋白抑制Gα（12）和Gα（13）信号传导，以及应用反义吗啉代修饰的寡核苷酸翻译干扰，会破坏汇聚延伸过程，而不改变胚胎模式。对中胚层细胞行为的分析表明，Gα（12/13）是汇聚过程中细胞伸长和有效背向迁移所必需的，且不依赖于非经典Wnt信号传导。此外，Gα（12/13）在细胞自主功能中，介导脊索延伸过程中插入作用背后的中外侧细胞伸长，可能与非经典Wnt信号传导平行发挥作用。这些发现提供了首个证据，表明Gα（12）和Gα（13）在驱动脊椎动物原肠胚形成的不同细胞行为中具有重叠且必不可少的作用。
