During development of the mammalian brain, cortical progenitors divide and give rise to neurons and glia. A number of signalling molecules and receptors are known to control neural progenitor fate but now (see p. 4335) Kamon Sanada and co-workers uncover a role for G protein-coupled receptor (GPCR) signalling during neurogenesis in the developing mouse neocortex. The authors demonstrate that GPRC5B, an orphan GPCR, is expressed in cortical progenitors of the developing mouse brain. Using RNAi-mediated knockdown, they report that GPRC5B is required for neuronal differentiation; GPRC5B-depleted progenitors fail to become neurons and instead adopt an astrocyte fate. The researchers further show that GPRC5B couples with the G12/13 class of heterotrimeric G proteins in cultured cells, and that GPRC5B signalling may converge with β-catenin signalling both in vitro and in vivo. In summary, these studies uncover a novel and important role for GPCR signalling during cortical neurogenesis, a finding that has significant implications for the therapeutic targeting and manipulation of stem cells.