期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 9, 页码 2723-2742出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2321-15.2016
关键词
ARID1B; chromatin remodeling complex; dendrite arborization; intellectual disability; spine
资金
- National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01-NS-091220]
- National Institute of General Medical Sciences of the National Institutes of Health [P20-GM-103471]
De novo truncating mutations in ARID1B, a chromatin-remodeling gene, cause Coffin-Siris syndrome, a developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated the neural functions of ARID1B during brain development. Here, we show that ARID1B regulates dendritic differentiation in the developing mouse brain. We knocked down ARID1B expression in mouse pyramidal neurons using in utero gene delivery methodologies. ARID1B knockdown suppressed dendritic arborization of cortical and hippocampal pyramidal neurons in mice. The abnormal development of dendrites accompanied a decrease in dendritic outgrowth into layer I. Furthermore, knockdown of ARID1B resulted in aberrant dendritic spines and synaptic transmission. Finally, ARID1B deficiency led to altered expression of c-Fos and Arc, and overexpression of these factors rescued abnormal differentiation induced by ARID1B knockdown. Our results demonstrate a novel role for ARID1B in neuronal differentiation and provide new insights into the origin of cognitive dysfunction associated with developmental intellectual disability.
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