气候变化领域集成服务门户(CCPortal): Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice

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DOI	10.1073/pnas.2009393118
	Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice
	Schlusche A.K.; Vay S.U.; Kleinenkuhnen N.; Sandke S.; Campos-Martín R.; Florio M.; Huttner W.; Tresch A.; Roeper J.; Rueger M.A.; Jakovcevski I.; Stockebrand M.; Isbrandt D.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:35
英文摘要	The development of the cerebral cortex relies on the controlled division of neural stem and progenitor cells. The requirement for precise spatiotemporal control of proliferation and cell fate places a high demand on the cell division machinery, and defective cell division can cause microcephaly and other brain malformations. Cell-extrinsic and -intrinsic factors govern the capacity of cortical progenitors to produce large numbers of neurons and glia within a short developmental time window. In particular, ion channels shape the intrinsic biophysical properties of precursor cells and neurons and control their membrane potential throughout the cell cycle. We found that hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits are expressed in mouse, rat, and human neural progenitors. Loss of HCN channel function in rat neural stem cells impaired their proliferation by affecting the cell-cycle progression, causing G1 accumulation and dysregulation of genes associated with human microcephaly. Transgene-mediated, dominant-negative loss of HCN channel function in the embryonic mouse telencephalon resulted in pronounced microcephaly. Together, our findings suggest a role for HCN channel subunits as a part of a general mechanism influencing cortical development in mammals. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Brain development; Cell cycle; HCN channelopathy; Microcephaly
语种	英语
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/238655
作者单位	German Center for Neurodegenerative Diseases, Bonn, 53175, Germany; Institute for Molecular and Behavioral Neuroscience, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, 50937, Germany; Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, 50937, Germany; Center for Molecular Neurobiology, University Hamburg, Hamburg, 20246, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, 01307, Germany; Center for Data and Simulation Science, University of Cologne, Cologne, 50937, Germany; Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, 60590, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, 50937, Germany
推荐引用方式 GB/T 7714	Schlusche A.K.,Vay S.U.,Kleinenkuhnen N.,et al. Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice[J],2021,118(35).
APA	Schlusche A.K..,Vay S.U..,Kleinenkuhnen N..,Sandke S..,Campos-Martín R..,...&Isbrandt D..(2021).Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice.Proceedings of the National Academy of Sciences of the United States of America,118(35).
MLA	Schlusche A.K.,et al."Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice".Proceedings of the National Academy of Sciences of the United States of America 118.35(2021).