Résumé
Wnt-11/Xfz7 signaling plays a major role in the regulation of convergent extension movements affecting the dorsal marginal zone (DMZ) of gastrulating
Xenopus embryos. In order to provide data concerning the molecular targets of Wnt-11/Xfz7 signals, we have analyzed the regulation of the Rho GTPase Cdc42 by Wnt-11. In animal cap ectoderm, Cdc42 activity increases as a response to Wnt-11 expression. This increase is inhibited by pertussis toxin, or sequestration of free Gβγ subunits by exogenous Gαi2 or Gαt. Activation of Cdc42 is also produced by the expression of bovine Gβ1 and Gγ2. This process is abolished by a PKC inhibitor, while phorbol esther treatment of ectodermal explants activates Cdc42 in a PKC-dependent way, implicating PKC downstream of Gβγ. In activin-treated animal caps and in the embryo, interference with Gβγ signaling rescues morphogenetic movements inhibited by Wnt-11 hyperactivation, thus phenocopying the dominant negative version of Cdc42 (N
17Cdc42). Conversely, expression of Gβ1γ2 blocks animal cap elongation. This effect is reversed by N
17Cdc42. Together, our results strongly argue for a role of Gβγ signaling in the regulation of Cdc42 activity downstream of Wnt-11/Xfz7 in mesodermal cells undergoing convergent extension. This idea is further supported by the observation that expression of Gαt in the DMZ causes severe gastrulation defects.