RRC ID 5609
Author Carreira-Barbosa F, Kajita M, Morel V, Wada H, Okamoto H, Martinez Arias A, Fujita Y, Wilson SW, Tada M.
Title Flamingo regulates epiboly and convergence/extension movements through cell cohesive and signalling functions during zebrafish gastrulation.
Journal Development
Abstract During vertebrate gastrulation, the body axis is established by coordinated and directional movements of cells that include epiboly, involution, and convergence and extension (C&E). Recent work implicates a non-canonical Wnt/planar cell polarity (PCP) pathway in the regulation of C&E. The Drosophila atypical cadherin Flamingo (Fmi) and its vertebrate homologue Celsr, a 7-pass transmembrane protein with extracellular cadherin repeats, regulate several biological processes, including C&E, cochlear cell orientation, axonal pathfinding and neuronal migration. Fmi/Celsr can function together with molecules involved in PCP, such as Frizzled (Fz) and Dishevelled (Dsh), but there is also some evidence that it may act as a cell adhesion molecule in a PCP-pathway-independent manner. We show that abrogation of Celsr activity in zebrafish embryos results in epiboly defects that appear to be independent of the requirement for Celsr in PCP signalling during C&E. Using a C-terminal truncated form of Celsr that inhibits membrane presentation of wild-type Celsr through its putative pro-region, a hanging drop assay reveals that cells from embryos with compromised Celsr activity have different cohesive properties from wild-type cells. It is disruption of this ability of Celsr to affect cell cohesion that primarily leads to the in vivo epiboly defects. In addition, Lyn-Celsr, in which the intracellular domain of Celsr is fused to a membrane localisation signal (Lyn), inhibits Fz-Dsh complex formation during Wnt/PCP signalling without affecting epiboly. Fmi/Celsr therefore has a dual role in mediating two separate morphogenetic movements through its roles in mediating cell cohesion and Wnt/PCP signalling during zebrafish gastrulation.
Volume 136(3)
Pages 383-92
Published 2009-2
DOI 10.1242/dev.026542
PII dev.026542
PMID 19091770
PMC PMC2687588
MeSH Adaptor Proteins, Signal Transducing / metabolism Amino Acid Sequence Animals Body Patterning / physiology Cadherins / genetics Cadherins / physiology* Cell Adhesion / physiology Cell Line Cell Membrane / physiology Cell Movement / physiology* Cell Polarity / physiology Dishevelled Proteins Drosophila Proteins Embryo, Nonmammalian / physiology Frizzled Receptors / metabolism Gastrulation / physiology* Humans Molecular Sequence Data Phosphoproteins / metabolism Protein Multimerization Receptors, G-Protein-Coupled / metabolism Signal Transduction / physiology Zebrafish / embryology* Zebrafish / metabolism Zebrafish Proteins / genetics Zebrafish Proteins / metabolism Zebrafish Proteins / physiology* src-Family Kinases / metabolism
IF 5.763
Times Cited 55
Zebrafish rw71 rw135