Wnt signalling required for expansion of neural crest and CNS progenitors

Abstract

Interactions between cells help to elaborate pattern within the vertebrate central nervous system (CNS)¹. The genes Wnt-1 and Wnt-3a, which encode members of the Wnt family of cysteine-rich secreted signals, are coexpressed at the dorsal midline of the developing neural tube, coincident with dorsal patterning^2,3. Each signal is essential for embryonic development, Wnt-1 for midbrain patterning^4,5 and Wnt-3a for formation of the paraxial mesoderm⁶, but the absence of a dorsal neural-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 tube⁷, 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 regulates the expansion of dorsal neural precursors. Given the widespread expression of different Wnt genes in discrete areas of the mammalian neural tube³, this may represent a general model for the action of Wnt signalling in the developing CNS.

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