期刊
JOURNAL OF NEUROSCIENCE
卷 31, 期 26, 页码 9772-9786出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1604-11.2011
关键词
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资金
- Epilepsy Foundation
- Welch Foundation [I-1660]
- Cancer Prevention and Research Institute of Texas [RP100674]
- National Institutes of Health [AG032383]
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.
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