β-Catenin Signaling Levels in Progenitors Influence the Laminar Cell Fates of Projection Neurons

The mechanisms underlying the timing of the laminar fate decisions during cortical neurogenesis remain poorly understood. Here we show that beta-catenin signaling in cortical neural precursors can regulate the laminar fate of their daughters. In ventricular zone neural precursors, beta-catenin signaling is higher when deep-layer neurons are being generated and lower when upper-layer neurons are being generated. Overactivation of beta-catenin in cortical precursors midway through corticogenesis increased the relative production of deep-layer neurons, while inhibition of signaling increased the relative production of upper-layer neurons. Furthermore, in late-gestation upper-layer precursors, overactive beta-catenin signaling was able to partially restore production of deep-layer neurons. These observations suggest that increased beta-catenin signaling can reset the timing of cortical precursors to promote the production of deep-layer neurons, while inhibition of beta-catenin signaling advances the timing to promote upper-layer production.