Work

REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation–differentiation balance in the developing brain

Year: 2017

Type: article

Abstract: Significance Nervous system development involves a delicate balance between neural progenitor proliferation and neuronal differentiation. Repressors and corepressors each affect this balance, but in many cases, existence of the complexes in vivo has not been shown. Here, we identify a repressor/corepressor complex in embryonic brain consisting of Insulinoma-associated 1 (INSM1) and the RE1 Silencing Transcription factor (REST) corepressors RCOR1 and RCOR2. Elimination of RCOR1 and RCOR2, or INSM1, robustly promotes neural proliferation over neuronal and oligodendrocyte differentiation. Further, their elimination results in overexpression of REST, a direct target gene of INSM1. Normalizing REST levels in the RCOR1/2-deficient brain partially restores aberrant brain morphology. Our results identify a repressor complex required for critical events during normal brain development.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1620230114