AI Article Synopsis
- Transcriptional regulation, particularly through histone deacetylase 9 (HDAC9), is crucial for the development and differentiation of neocortical neurons.
- Increased neuronal firing activity triggers the movement of HDAC9 from the nucleus to the cytoplasm, influencing gene expression and neuron structure.
- Mutating HDAC9 prevents this translocation, leading to reduced dendritic growth and altered expression of specific genes, suggesting that HDAC9 plays a significant role in neuron development through chromatin remodeling.
Article Abstract
Transcriptional regulation of gene expression is thought to play a pivotal role in activity-dependent neuronal differentiation and circuit formation. Here, we investigated the role of histone deacetylase 9 (HDAC9), which regulates transcription by histone modification, in the development of neocortical neurons. The translocation of HDAC9 from nucleus to cytoplasm was induced by an increase of spontaneous firing activity in cultured mouse cortical neurons. This nucleocytoplasmic translocation was also observed in postnatal development in vivo. The translocation-induced gene expression and cellular morphology was further examined by introducing an HDAC9 mutant that disrupts the nucleocytoplasmic translocation. Expression of c-fos, an immediately-early gene, was suppressed in the mutant-transfected cells regardless of neural activity. Moreover, the introduction of the mutant decreased the total length of dendritic branches, whereas knockdown of HDAC9 promoted dendritic growth. These findings indicate that chromatin remodeling with nucleocytoplasmic translocation of HDAC9 regulates activity-dependent gene expression and dendritic growth in developing cortical neurons.
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| http://dx.doi.org/10.1111/j.1460-9568.2010.07218.x | DOI Listing |
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