Neurogenesis in the neocortex is a highly coordinated process that occurs during specific developmental stages. Balancing neural progenitor cell (NPC) self-renewal and their differentiation into mature neurons is a crucial aspect in this process that needs to be carefully controlled. The canonical Wnt–β-catenin signalling pathway is known to be important for regulating cell fate during neurogenesis. However, less is known about the role of non-canonical (β-catenin-independent) Wnt signalling pathways, which are activated by Wnt5a and receptor-tyrosine-kinase-like orphan receptors (ROR) 1 and 2. On page , Mitsuharu Endo, Yasuhiro Minami and colleagues now describe a function for ROR1 and ROR2 in maintenance of the NPC population during neocortical neurogenesis. Specifically, Wnt5a signalling through ROR1 and ROR2 is involved in generating neurons by preserving the pool of proliferative neurogenic NPCs. Binding of Wnt5a to either ROR receptor leads to the phosphorylation of disheveled 2 (DVL2) but does not activate signalling pathways that involve β-catenin. Furthermore, the authors illustrate that ROR1 and ROR2, as well as DVL2, are required for the maintenance of NPCs in the developing mouse neocortex. Overall, these results highlight an important role for the non-canonical Wnt signalling pathway in regulating NPC proliferation during brain development.
