Galpha12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton

• Published in: The Journal of cell biology Vol. 184; no. 6; pp. 909 - 921
• Main Authors: Lin, Fang, Chen, Songhai, Sepich, Diane S, Panizzi, Jennifer Ray, Clendenon, Sherry G, Marrs, James A, Hamm, Heidi E, Solnica-Krezel, Lilianna
• Format: Journal Article
• Language: English
• Published: United States 23.03.2009
• Subjects: Actins - metabolism; Animals; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion; Cell Movement; Cytoskeleton - enzymology; Cytoskeleton - metabolism; Gastrula - enzymology; Gastrula - metabolism; Gastrulation; Gene Expression Regulation, Developmental; GTP-Binding Protein alpha Subunits, G12-G13 - genetics; GTP-Binding Protein alpha Subunits, G12-G13 - metabolism; Guanine Nucleotide Exchange Factors - metabolism; Mutation; Protein Structure, Tertiary; Recombinant Fusion Proteins - metabolism; rho GTP-Binding Proteins - metabolism; Signal Transduction; Time Factors; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1540-8140
• DOI: 10.1083/jcb.200805148

Epiboly spreads and thins the blastoderm over the yolk cell during zebrafish gastrulation, and involves coordinated movements of several cell layers. Although recent studies have begun to elucidate the processes that underlie these epibolic movements, the cellular and molecular mechanisms involved remain to be fully defined. Here, we show that gastrulae with altered Galpha(12/13) signaling display delayed epibolic movement of the deep cells, abnormal movement of dorsal forerunner cells, and dissociation of cells from the blastoderm, phenocopying e-cadherin mutants. Biochemical and genetic studies indicate that Galpha(12/13) regulate epiboly, in part by associating with the cytoplasmic terminus of E-cadherin, and thereby inhibiting E-cadherin activity and cell adhesion. Furthermore, we demonstrate that Galpha(12/13) modulate epibolic movements of the enveloping layer by regulating actin cytoskeleton organization through a RhoGEF/Rho-dependent pathway. These results provide the first in vivo evidence that Galpha(12/13) regulate epiboly through two distinct mechanisms: limiting E-cadherin activity and modulating the organization of the actin cytoskeleton.