气候变化领域集成服务门户(CCPortal): Dlk1 dosage regulates hippocampal neurogenesis and cognition

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DOI	10.1073/PNAS.2015505118
	Dlk1 dosage regulates hippocampal neurogenesis and cognition
	Montalbán-Loro R.; Lassi G.; Lozano-Ureña A.; Perez-Villalba A.; Jiménez-Villalba E.; Charalambous M.; Vallortigara G.; Horner A.E.; Saksida L.M.; Bussey T.J.; Trejo J.L.; Tucci V.; Ferguson-Smith A.C.; Ferrón S.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	Neurogenesis in the adult brain gives rise to functional neurons, which integrate into neuronal circuits and modulate neural plasticity. Sustained neurogenesis throughout life occurs in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus and is hypothesized to be involved in behavioral/cognitive processes such as memory and in diseases. Genomic imprinting is of critical importance to brain development and normal behavior, and exemplifies how epigenetic states regulate genome function and gene dosage. While most genes are expressed from both alleles, imprinted genes are usually expressed from either the maternally or the paternally inherited chromosome. Here, we show that in contrast to its canonical imprinting in nonneurogenic regions, Delta-like homolog 1 (Dlk1) is expressed biallelically in the SGZ, and both parental alleles are required for stem cell behavior and normal adult neurogenesis in the hippocampus. To evaluate the effects of maternally, paternally, and biallelically inherited mutations within the Dlk1 gene in specific behavioral domains, we subjected Dlk1-mutant mice to a battery of tests that dissociate and evaluate the effects of Dlk1 dosage on spatial learning ability and on anxiety traits. Importantly, reduction in Dlk1 levels triggers specific cognitive abnormalities that affect aspects of discriminating differences in environmental stimuli, emphasizing the importance of selective absence of imprinting in this neurogenic niche. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Behavior; Gene dosage; Genomic imprinting; Hippocampus; Neurogenesis
语种	英语
scopus关键词	glial fibrillary acidic protein; Ki 67 antigen; transcription factor Sox2; adult; allele; animal experiment; animal model; animal tissue; anxiety; Article; biallelic expression; brain development; C57BL 6 mouse; cell differentiation; cell function; cell membrane potential; cell proliferation; cell self-renewal; chromosome; cognition; controlled study; Dlk1 gene; elevated plus maze test; environmental factor; epigenetics; gene; gene deletion; gene dosage; gene expression; gene expression regulation; gene function; gene mutation; genome imprinting; genotype; hemizygosity; heterozygosity; hippocampus; homozygosity; in vivo study; maternal inheritance; Meg3 gene; memory consolidation; memory disorder; mouse; mouse mutant; nerve cell plasticity; nervous system development; nonhuman; paternal inheritance; phenotype; priority journal; single nucleotide polymorphism; Snrpn gene; spatial learning; spatial memory; stem cell; subgranular zone; wild type mouse
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/181178
作者单位	ERI Biotecmed-Departamento de Biología Celular, Universidad de Valencia, Valencia, 46010, Spain; Genetics and Epigenetics of Behaviour (GEB) Laboratory, Istituto Italiano di Tecnologia, Genova, 16163, Italy; Translational Science and Experimental Medicine Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge Biomedical Campus, Cambridge, CB2 0AA, United Kingdom; Faculty of Psychology, Laboratory of Animal Behavior Phenotype (LABP), Universidad Católica de Valencia, Valencia, 46100, Spain; Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, United Kingdom; Center for Mind/Brain Sciences, University of Trento, Rovereto TN, 38068, Italy; Synome Ltd, Babraham, Cambridge, CB22 3AT, United Kingdom; Department of Psychology, Medical Research Council, Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, United Kingdom; Molecular Medicine Research Laboratories, Robarts Research Institute, S...
推荐引用方式 GB/T 7714	Montalbán-Loro R.,Lassi G.,Lozano-Ureña A.,et al. Dlk1 dosage regulates hippocampal neurogenesis and cognition[J],2021,118(11).
APA	Montalbán-Loro R..,Lassi G..,Lozano-Ureña A..,Perez-Villalba A..,Jiménez-Villalba E..,...&Ferrón S.R..(2021).Dlk1 dosage regulates hippocampal neurogenesis and cognition.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Montalbán-Loro R.,et al."Dlk1 dosage regulates hippocampal neurogenesis and cognition".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).