ZFIN ID: ZDB-PUB-100302-20
RPTPalpha and PTPepsilon Signaling via Fyn/Yes and RhoA is Essential for Zebrafish Convergence and Extension Cell Movements during Gastrulation
van Eekelen, M., Runtuwene, V., Overvoorde, J., and den Hertog, J.
Date: 2010
Source: Developmental Biology   340(2): 626-639 (Journal)
Registered Authors: den Hertog, Jeroen, Overvoorde, John
Keywords: Zebrafish, Protein-tyrosine phosphatase, RPTPα, PTPε, Src family kinases, Convergence and extension cell movements, Gastrulation
MeSH Terms:
  • Animals
  • Cell Movement/physiology
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/physiology
  • Gastrulation/physiology*
  • Monomeric GTP-Binding Proteins/genetics
  • Monomeric GTP-Binding Proteins/physiology*
  • Proto-Oncogene Proteins c-fyn/genetics
  • Proto-Oncogene Proteins c-fyn/physiology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4/physiology*
  • Signal Transduction/physiology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • rhoA GTP-Binding Protein/genetics
  • rhoA GTP-Binding Protein/physiology*
PubMed: 20188722 Full text @ Dev. Biol.
Convergence and extension (C&E) cell movements are essential to shape the body axis during vertebrate gastrulation. We have used the zebrafish to assess the role of the receptor protein-tyrosine phosphatases, RPTPalpha and PTPepsilon, in gastrulation cell movements. Both RPTPalpha and PTPepsilon knockdown and ptpra(-/-) embryos show defects in C&E movements. A method was developed to track gastrulation cell movements using confocal microscopy in a quantitative manner and ptpra(-/-) embryos displayed reduced convergence as well as extension speeds. RPTPalpha and PTPepsilon knockdowns cooperated with knockdown of a well known factor in C&E cell movement, non-canonical Wnt11. RPTPalpha and PTPepsilon dephosphorylate and activate Src family kinases in various cell types in vitro and in vivo. We found that Src family kinase phosphorylation was enhanced in ptpra(-/-) embryos, consistent with reduced Src family kinase activity. Importantly, both ptpra(-/-) as well as RPTPalpha and PTPepsilon knockdown induced C&E defects were rescued by active Fyn and Yes. Moreover, active RhoA rescued the RPTPalpha and PTPepsilon knockdown and ptpra(-/-) induced gastrulation cell movement defects as well. Our results demonstrate that RPTPalpha and PTPepsilon are essential for C&E movements in a signaling pathway parallel to non-canonical Wnts and upstream of Fyn, Yes and RhoA.