Wnt signals are targets and mediators of Gli function

There is growing evidence that Gli proteins participate in the mediation of Hedgehog and FGF signaling in neural and mesodermal development. However, little is known about which genes act downstream of Gli proteins, Here we s how the regulation of members of the Wnt family by Gli proteins in differen t contexts. Our findings indicate that Gli2 regulates Wnt8 expression in th e ventral marginal zone of the early frog embryo: activating Gli2 construct s induce ectopic Wnt8 expression in animal cap explants, whereas repressor forms inhibit its endogenous expression in the marginal zone. Using truncat ed Frizzled and dominant-negative Wnt constructs, we then show the requirem ent of at least two Wnt proteins, Wnt8 and Wnt11, for Gli2/ 3-induced poste rior mesodermal development. Blocking Wnt signals, however, inhibits Gli2/3 -induced morphogenesis, but not mesodermal specification, Gli2/3 may theref ore normally coordinate the action of these two Wnt proteins, which regulat e distinct downstream pathways. In addition, the finding that Gli1 consiste ntly induces a distinct set of Wnt genes in animal cap explants and in skin tumors suggests that Wnt regulation by Gli proteins is general, Such a mec hanism may link signals that induce Gli activity, such as pops and Hedgehog s, with Wnt function.