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

Lin F, Chen S, Sepich DS, Panizzi JR, Clendenon SG, Marrs JA, Hamm HE, Solnica-Krezel L
J Cell Biol. 2009 184 (6): 909-21

PMID: 19307601 · PMCID: PMC2664974 · 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.

MeSH Terms (19)

Actins Animals Cadherins Cell Adhesion Cell Movement Cytoskeleton Gastrula Gastrulation Gene Expression Regulation, Developmental GTP-Binding Protein alpha Subunits, G12-G13 Guanine Nucleotide Exchange Factors Mutation Protein Structure, Tertiary Recombinant Fusion Proteins rho GTP-Binding Proteins Signal Transduction Time Factors Zebrafish Zebrafish Proteins

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