Activation of Gbetagamma signaling downstream of Wnt-11/Xfz7 regulates Cdc42 activity during Xenopus gastrulation.
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 Gbetagamma subunits by exogenous Galphai2 or Galphat. Activation of Cdc42 is also produced by the expression of bovine Gbeta1 and Ggamma2. 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 Gbetagamma. In activin-treated animal caps and in the embryo, interference with Gbetagamma signaling rescues morphogenetic movements inhibited by Wnt-11 hyperactivation, thus phenocopying the dominant negative version of Cdc42 (N(17)Cdc42). Conversely, expression of Gbeta1gamma2 blocks animal cap elongation. This effect is reversed by N(17)Cdc42. Together, our results strongly argue for a role of Gbetagamma 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 Galphat in the DMZ causes severe gastrulation defects.
Laboratoire de Biologie du Dévelopment, groupe Biologie Expérimentale, UMR CNRS 7622, Université Paris VI, 9 quai Saint-Bernard, 75005 Paris, France.
Alfredo
A
Penzo-Mendèz
Muriel
M
Umbhauer
Alexandre
A
Djiane
Jean-Claude
JC
Boucaut
Jean-François
JF
Riou
D028341:Activins / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000072261:Dishevelled Proteins; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D005775:Gastrula / Q000187:drug effects / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D004791:Enzyme Inhibitors; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D006023:Glycoproteins; D010750:Phosphoproteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; C512785:wnt11b protein, Xenopus; D028341:Activins; D037342:Pertussis Toxin; D011493:Protein Kinase C; D020962:Heterotrimeric GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein