Essential Roles for ARID1B in Dendritic Arborization and Spine Morphology of Developing Pyramidal Neurons

• DOI: 10.1523/jneurosci.2321-15.2016
• Publication Date: 2016-03-02T16:53:55Z
• Authors: Minhan Ka; Divyan A. Chopra; Shashank M. Dravid; Woo-Yang Kim
• Keywords: 0303 health sciences; Neuronal Plasticity; Patch-Clamp Techniques; Dendritic Spines; Pyramidal Cells; Action Potentials; Brain; Gene Expression Regulation, Developmental; Nuclear Proteins; Embryo, Mammalian; DNA-Binding Proteins; Mice; 03 medical and health sciences; Animals, Newborn; Pregnancy; Glial Fibrillary Acidic Protein; Animals; Humans; Female; Microtubule-Associated Proteins; Cells, Cultured; Transcription Factors

De novo truncating mutations in ARID1B , a chromatin-remodeling gene, cause Coffin–Siris syndrome, developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated neural functions of during brain development. Here, show that regulates dendritic differentiation developing mouse brain. We knocked down expression pyramidal neurons using utero gene delivery methodologies. knockdown suppressed arborization cortical hippocampal mice. The abnormal development dendrites accompanied decrease outgrowth into layer I. Furthermore, resulted aberrant spines synaptic transmission. Finally, deficiency led altered c-Fos Arc, overexpression these factors rescued induced knockdown. Our results demonstrate novel role for neuronal provide new insights origin associated with disability. SIGNIFICANCE STATEMENT Haploinsufficiency ARID1B, component chromatin remodeling complex, causes However, is required brain, such as synapse formation. findings suggest plays critical establishment circuitry regulating complexity. may via wiring defective neurons.