ZFIN ID: ZDB-PUB-090105-1
Flamingo regulates epiboly and convergence/extension movements through cell cohesive and signalling functions during zebrafish gastrulation
Carreira-Barbosa, F., Kajita, M., Morel, V., Wada, H., Okamoto, H., Martinez Arias, A., Fujita, Y., Wilson, S.W., and Tada, M.
Date: 2009
Source: Development (Cambridge, England)   136(3): 383-392 (Journal)
Registered Authors: Okamoto, Hitoshi, Tada, Masazumi, Wada, Hironori, Wilson, Steve
Keywords: Epiboly, Convergent extension, Planar cell polarity, Celsr, Flamingo, Drosophila, Zebrafish
MeSH Terms:
  • 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
  • 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
PubMed: 19091770 Full text @ Development
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.