RGS family members art GTPase activating proteins (GAPs) that antagonize si
gnaling by heterotrimeric G proteins, Injection of Xenopus embryos with RNA
encoding rat RGS4 (rRGS4), a GAP for G(i) and G(q), resulted in shortened
trunks and decreased skeletal muscle. This phenotype is nearly identical to
the effect of injection of either frzb or dominant negative Xwnt-8. Inject
ion of human RGS2, which selectively deactivates Go, had similar effects, r
RGS4 inhibited the ability of early Xwnt-8 but not Xdsh misexpression to ca
use axis duplication. This effect is distinct from axin family members that
contain RGS-like domains but act downstream of Xdsh, We identified two Xen
opus RGS4 homologs, one of which, Xrgs4a, was expressed as a Spemann organi
zer component. Injection of Xenopus embryos with Xrgs4a also resulted in sh
ortened trunks and decreased skeletal muscle. These results suggest that RG
S proteins modulate Xwnt-8 signaling by attenuating the function of a G pro
tein.