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 language | English |
|---|---|
| Pages (from-to) | 2723-2742 |
| Number of pages | 20 |
| Journal | Journal of Neuroscience |
| Volume | 36 |
| Issue number | 9 |
| DOIs | |
| State | Published - Mar 2 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Essential roles for ARID1B in dendritic arborization and spine morphology of developing pyramidal neurons
AU - Ka, Minhan
AU - Chopra, Divyan A.
AU - Dravid, Shashank M.
AU - Kim, Woo Yang
PY - 2016/3/2
Y1 - 2016/3/2
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84959548831&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2321-15.2016
DO - 10.1523/JNEUROSCI.2321-15.2016
M3 - Article
VL - 36
SP - 2723
EP - 2742
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 9
ER -