RPTPα and PTPε signaling via Fyn/Yes and RhoA is essential for zebrafish convergence and extension cell movements during gastrulation

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. RPTP alpha and PTP epsilon, in gastrulation cell movements. Both RPTP alpha and PTP epsilon 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. RPTP alpha and PTP epsilon knockdowns cooperated with knockdown of a well known factor in C&E cell movement, non-canonical Wnt11. RPTP alpha and PTP epsilon 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(-/-) and RPTP alpha and PTP epsilon knockdown induced C&E defects were rescued by active Fyn and Yes. Moreover, active RhoA rescued the RPTP alpha and PTP epsilon knockdown and ptpra(-/-) induced gastrulation cell movement defects as well. Our results demonstrate that RPTP alpha and PTP epsilon are essential for C&E movements in a signaling pathway parallel to non-canonical Wnts and upstream of Fyn, Yes and RhoA. (C) 2010 Elsevier Inc. All rights reserved.