| First Author | Gao Z | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 26 | Pages | 9772-86 |
| PubMed ID | 21715642 | Mgi Jnum | J:174056 |
| Mgi Id | MGI:5051842 | Doi | 10.1523/JNEUROSCI.1604-11.2011 |
| Citation | Gao Z, et al. (2011) The Master Negative Regulator REST/NRSF Controls Adult Neurogenesis by Restraining the Neurogenic Program in Quiescent Stem Cells. J Neurosci 31(26):9772-86 |
| abstractText | Transcriptional regulation is a critical mechanism in the birth, specification, and differentiation of granule neurons in the adult hippocampus. One of the first negative-acting transcriptional regulators implicated in vertebrate development is repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF)-thought to regulate hundreds of neuron-specific genes-yet its function in the adult brain remains elusive. Here we report that REST/NRSF is required to maintain the adult neural stem cell (NSC) pool and orchestrate stage-specific differentiation. REST/NRSF recruits CoREST and mSin3A corepressors to stem cell chromatin for the regulation of pro-neuronal target genes to prevent precocious neuronal differentiation in cultured adult NSCs. Moreover, mice lacking REST/NRSF specifically in NSCs display a transient increase in adult neurogenesis that leads to a loss in the neurogenic capacity of NSCs and eventually diminished granule neurons. Our work identifies REST/NRSF as a master negative regulator of adult NSC differentiation and offers a potential molecular target for neuroregenerative approaches. |
