Galpha12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton
- Lin, F., Chen, S., Sepich, D.S., Panizzi, J.R., Clendenon, S.G., Marrs, J.A., Hamm, H.E., and Solnica-Krezel, L.
- The Journal of cell biology 184(6): 909-921 (Journal)
- Registered Authors
- Clendenon, Sherry, Lin, Fang, Marrs, James A., Panizzi, Jennifer R., Sepich, Diane, Solnica-Krezel, Lilianna
- MeSH Terms
- Cell Adhesion
- Cell Movement
- GTP-Binding Protein alpha Subunits, G12-G13/genetics
- GTP-Binding Protein alpha Subunits, G12-G13/metabolism*
- Gene Expression Regulation, Developmental
- Guanine Nucleotide Exchange Factors/metabolism
- Protein Structure, Tertiary
- Recombinant Fusion Proteins/metabolism
- Signal Transduction*
- Time Factors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- rho GTP-Binding Proteins/metabolism
- 19307601 Full text @ J. Cell Biol.
Lin, F., Chen, S., Sepich, D.S., Panizzi, J.R., Clendenon, S.G., Marrs, J.A., Hamm, H.E., and Solnica-Krezel, L. (2009) Galpha12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton. The Journal of cell biology. 184(6):909-921.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes