Summary
Cerebral cortex expansion in development and evolution is defined by the spatiotemporal production of neurons. Although the intracellular mechanisms regulating the decision of radial glial cells (RGCs) to self-amplify or produce neurons are beginning to be deciphered, the upstream signalling pathways involved are less well understood. Here we highlight an evolutionarily conserved role of the canonical BMP pathway in controlling neurogenesis and growth during corticogenesis. Through gain- and loss-of-function experiments on chick embryos, we found that the activity of the BMP effectors SMAD1/5 supports RGC self-amplification and impedes their premature differentiation and exhaustion. The microcephaly and overall growth retardation observed in conditional Smad1/5wt/fl;Nestin:Cre+/0 (SmadNes) mutant mice reveal this role to be evolutionarily conserved. Furthermore, we demonstrate that the effect of SMAD1/5 on RGCs depends on the activity of the Hippo signaling effector YAP. We anticipate this SMAD1/5-YAP signaling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.
