WNT SIGNALING REQUIRED FOR EXPANSION OF NEURAL CREST AND CNS PROGENITORS

Interactions between cells help to elaborate pattern within the verteb rate central nervous system (CNS)(1). The genes Wnt-1 and Wnt-3a, whic h encode members of the Wnt family of cysteine-rich secreted signals, are coexpressed at the dorsal midline of the developing neural tube, c oincident with dorsal patterning(2,3). Each signal is essential for em bryonic development, Wnt-1 for midbrain patterning(4,5) and Wnt-3a for formation of the paraxial mesoderm(6), but the absence of a dorsal ne ural-tube phenotype in each mutant suggests that Wnt signalling may be redundant. Here we demonstrate that in the absence of both Wnt-1 and Wnt-3a there is a marked deficiency in neural crest derivatives, which originate from the dorsal neural tube(7), and a pronounced reduction in dorsolateral neural precursors within the neural tube itself. These phenotypes do not seem to result from a disruption in the mechanisms responsible for establishing normal dorsoventral polarity. Rather, our results are consistent with a model in which local Wnt signalling reg ulates the expansion of dorsal neural precursors. Given the widespread expression of different Wnt genes in discrete areas of the mammalian neural tube(3), this may represent a general model for the action of W nt signalling in the developing CNS.