In a study published in Nature communications, the group of André Goffinet, Investigator at UCL, shows that immature neurons regulate the fate of apical progenitors through Wnt7–Celsr3–Fzd3 signalling.
Sequential generation of neurons and glial cells during development is critical for the wiring and function of the cerebral cortex. This process requires accurate coordination of neural progenitor cell (NPC) fate decisions, by NPC-autonomous mechanisms as well as by negative feedback from neurons. The switch between production of neurons and production of glial cells is regulated by various signaling pathways, among which Notch plays a prominent role.
The group of André Goffinet shows that neurogenesis is protracted and gliogenesis decreased in mice with mutations of genes Celsr3 and Fzd3, 2 genes involved in the regulation of Planar Cell Polarity. This phenotype is due to gene inactivation in young cortical neurons. Mutant neurons are unable to respond to secreted factor Wnt7, and to regulate Notch signalling in NPC. Thus, Celsr3 and Fzd3 enable neurons to send feedback signals to NPC that tune their fate decisions via Notch activation.
Wang et al, Feedback regulation of apical progenitor fate by immature neurons through Wnt7-Celsr3-Fzd3 signalling, Nature Commnications (2016) 7:10936. doi: 10.1038/ncomms10936.