Essential roles for ARID1B in dendritic arborization and spine morphology of developing pyramidal neurons

Minhan Ka, Divyan A. Chopra, Shashank M. Dravid, Woo Yang Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2723-2742
Number of pages20
JournalJournal of Neuroscience
Volume36
Issue number9
DOIs
StatePublished - Mar 2 2016

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Dendritic Spines
Neuronal Plasticity
Pyramidal Cells
Intellectual Disability
Developmental Disabilities
Chromatin Assembly and Disassembly
Brain
Dendrites
Synaptic Transmission
Genes
Mutation
Cognitive Dysfunction

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Essential roles for ARID1B in dendritic arborization and spine morphology of developing pyramidal neurons. / Ka, Minhan; Chopra, Divyan A.; Dravid, Shashank M.; Kim, Woo Yang.

In: Journal of Neuroscience, Vol. 36, No. 9, 02.03.2016, p. 2723-2742.

Research output: Contribution to journalArticle

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