Ga12/13 signaling regulates epiboly by inhibiting E‐cadherin function

Epiboly is the first morphogenetic movement of the zebrafish embryo, which spreads and thins the blastoderm to completely enclose the yolk cell. Normal epiboly coordinates movements of the deep cells, the enveloping layer, and the yolk syncytial layer. E‐cadherin has been shown to be vital for this epibolic movement, as embryos harboring mutations in E‐cadherin gene or injected with E‐cadherin MOs displayed severe epiboly delay or arrest. However, how the function of E‐cadherin is regulated remains unknown. Here we show that epiboly is impaired in embryos with excessive or reduced Gα 12/13 expression. In particular, deep cells migrated slower towards the vegetal pole, while epibolic movement of enveloping layer, dorsal forerunner cells and yolk syncytial nuclei progressed normally. Similar phenotypic changes were found in E‐cadherin mutant embryos, suggesting a possible linkage between Gα 12/13 and E‐cadherin signaling pathways. Indeed, suppression of Gα 12 or Gα 13 partially rescued, while increased Gα 13 signaling exacerbated epiboly defects of the E‐cadherin mutants. Moreover, immunoprecipitation studies indicated that Gα 13 formed a complex with the C‐terminus of E‐cadherin. These results thus provide the first in vivo evidence that Gα 12/13 signaling may affect epiboly probably by negatively regulating E‐cadherin functions.