Wnt signaling determines ventral spinal cord cell fates in a time-dependent manner

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Abstract
The identity of distinct cell types in the ventral neural tube is generally believed to be specified by sonic hedgehog (Shh) in a concentration-dependent manner. However, recent studies have questioned whether Shh is the sole signaling molecule determining ventral neuronal cell fates. Here we provide evidence that canonical Wnt signaling is involved in the generation of different cell types in the ventral spinal cord. We show that Wnt signaling is active in the mouse ventral spinal cord at the time when ventral cell types are specified. Furthermore, using an approach that stabilizes β-catenin protein in small patches of ventral spinal cord cells at different stages, we show that Wnt signaling activates different subsets of target genes depending on the time when Wnt signaling is amplified. Moreover, disruption of Wnt signaling results in the expansion of ventrally located progenitors. Finally, we show genetically that Wnt signaling interacts with Hh signaling at least in part through regulating the transcription of Gli3. Our results reveal a novel mechanism by which ventral patterning is achieved through a coordination of Wnt and Shh signaling.