The cytoplasmic tyrosine kinase Arg regulates Xenopus gastrulation via the adaptor protein CrkII.

CHENBEI CHANG, JASON FLETCHER, HARSHIT DWIVEDI, MADHAV DEVANI, GUSTAVO BONACCI

Albuquerque

Congreso; Society for Developmental Biology 69th Annual Meeting; 2010

Society for Developmental Biology Jointly with the Japanese Society of Developmental Biologists

Coordinated cell movements during vertebrate gastrulation are crucial for correct placement of embryonic tissues along body axes and are controlled by multiple signals. While non-canonical Wnt pathway is shown to regulate cell polarity and directional cell behaviors via the cytoplasmic protein Dishevelled, the mechanisms used by receptor tyrosine kinases, such as PDGFR, FGFR and ErbBs, tomodulate gastrulation are less understood. Here, we show that the actin-binding cytoplasmic tyrosine kinase Arg modulates cell movements during Xenopus gastrulation. Arg was expressed in dorsal tissues at the onset of gastrulation, and both gain- and loss-of-function of Arg disrupted gastrulation movements and led to defective frog tadpoles. Overexpression of Arg inhibited head mesoderm migration effectively, while reduction of Arg by specific antisense morpholino oligos caused aberrant head mesoderm migration, resulting in reduced migratory distance and increased cell dissociation. Both overexpression and depletion of Arg also affected convergent extension movements. The regulation of Xenopus gastrulation by Arg required an intact kinase domain, but the actin-binding motif could be dispensed. Arg controlled phosphorylation of endogenous CrkII, an adaptor protein involved in activation of Rho family GTPases and actin reorganization. Our data thus imply that Argmay be an essentialmediator of receptor tyrosine kinases during gastrulation and can modulate cell movements via phosphorylation of an important effector CrkII.