气候变化领域集成服务门户(CCPortal): Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity

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DOI	10.1073/pnas.2100686118
	Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity
	Doyle D.Z.; Lam M.M.; Qalieh A.; Qalieh Y.; Sorel A.; Funk O.H.; Kwan K.Y.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:21
英文摘要	Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	axon pathfinding; Cerebral cortex; chromatin regulation; development; neural circuits
语种	英语
scopus关键词	protein Arid1a; regulator protein; unclassified drug; animal cell; animal experiment; Arid1a gene; Article; axon; axon fasciculation; axon guidance; brain cortex; brain development; chromatin; controlled study; corpus callosum agenesis; embryo; extracellular matrix; gene deletion; gene disruption; gene expression; gene function; genetic regulation; gray matter; innervation; mouse; nerve cell; neuroanatomy; nonhuman; phenotype; protein expression; regulator gene; subplate neuron; thalamocortical neuron; whisker barrel development; white matter
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238914
作者单位	Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, United States; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Doyle D.Z.,Lam M.M.,Qalieh A.,et al. Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity[J],2021,118(21).
APA	Doyle D.Z..,Lam M.M..,Qalieh A..,Qalieh Y..,Sorel A..,...&Kwan K.Y..(2021).Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity.Proceedings of the National Academy of Sciences of the United States of America,118(21).
MLA	Doyle D.Z.,et al."Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021).