Constitutive activity of a G protein-coupled receptor, DRD1, contributes to human cerebral organoid formation.

ABSTRACT: The intricate balance of neural stem cell (NSC) amplification and neurogenesis is central to nervous system development. Dopamine D1 receptor (DRD1) is a typical G protein-coupled receptor (GPCR) mainly expressed in neurogenic area, with high constitutive activity. The receptor appears in the embryonic period before the formation of mature synaptic contacts, which indicates that dopamine receptor and its constitutive activity play crucial roles in the embryonic brain development. Here, we found that DRD1 was enriched in human NSCs. Inhibition of the receptor activity by its inverse agonists promoted human NSCs proliferation and impeded its differentiation. These results were also mimicked by genetic knockdown of DRD1, which also blocked the effects of inverse agonists, suggesting a recepto

SUBMITTER: Wang Q 

PROVIDER: S-EPMC7384186 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature