Home > Publications Database > Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice. > print

001     162815
005     20230915092409.0
024 7 _ |a 10.1073/pnas.2009393118
|2 doi
024 7 _ |a pmid:34429357
|2 pmid
024 7 _ |a pmc:PMC8536352
|2 pmc
024 7 _ |a 0027-8424
|2 ISSN
024 7 _ |a 1091-6490
|2 ISSN
024 7 _ |a altmetric:112353673
|2 altmetric
037 _ _ |a DZNE-2021-01470
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Schlusche, Anna Katharina
|0 P:(DE-2719)2810985
|b 0
|e First author
|u dzne
245 _ _ |a Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice.
260 _ _ |a Washington, DC
|c 2021
|b National Acad. of Sciences
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1637592926_15705
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a 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.
536 _ _ |a 351 - Brain Function (POF4-351)
|0 G:(DE-HGF)POF4-351
|c POF4-351
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a HCN channelopathy
|2 Other
650 _ 7 |a brain development
|2 Other
650 _ 7 |a cell cycle
|2 Other
650 _ 7 |a microcephaly
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cell Cycle
|2 MeSH
650 _ 2 |a Cell Death
|2 MeSH
650 _ 2 |a Cell Proliferation: physiology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Cerebral Cortex: cytology
|2 MeSH
650 _ 2 |a Cerebral Cortex: embryology
|2 MeSH
650 _ 2 |a Channelopathies: embryology
|2 MeSH
650 _ 2 |a Channelopathies: etiology
|2 MeSH
650 _ 2 |a Embryonic Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Embryonic Stem Cells: physiology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: genetics
|2 MeSH
650 _ 2 |a Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: metabolism
|2 MeSH
650 _ 2 |a Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: physiology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Microcephaly: embryology
|2 MeSH
650 _ 2 |a Microcephaly: etiology
|2 MeSH
650 _ 2 |a Neural Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Neural Stem Cells: physiology
|2 MeSH
650 _ 2 |a Neurogenesis: physiology
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
700 1 _ |a Vay, Sabine Ulrike
|0 0000-0002-3289-7807
|b 1
700 1 _ |a Kleinenkuhnen, Niklas
|b 2
700 1 _ |a Sandke, Steffi
|b 3
700 1 _ |a Campos-Martín, Rafael
|b 4
700 1 _ |a Florio, Marta
|0 0000-0002-6168-005X
|b 5
700 1 _ |a Huttner, Wieland
|0 0000-0003-4143-7201
|b 6
700 1 _ |a Tresch, Achim
|0 0000-0002-4146-6371
|b 7
700 1 _ |a Roeper, Jochen
|b 8
700 1 _ |a Rueger, Maria Adele
|0 0000-0001-8036-395X
|b 9
700 1 _ |a Jakovcevski, Igor
|0 P:(DE-2719)2811046
|b 10
|u dzne
700 1 _ |a Stockebrand, Malte
|0 P:(DE-2719)2810965
|b 11
|u dzne
700 1 _ |a Isbrandt, Dirk
|0 P:(DE-2719)2810976
|b 12
|e Last author
|u dzne
773 _ _ |a 10.1073/pnas.2009393118
|g Vol. 118, no. 35, p. e2009393118 -
|0 PERI:(DE-600)1461794-8
|n 35
|p e2009393118
|t Proceedings of the National Academy of Sciences of the United States of America
|v 118
|y 2021
|x 1091-6490
909 C O |o oai:pub.dzne.de:162815
|p VDB
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)2810985
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 10
|6 P:(DE-2719)2811046
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 11
|6 P:(DE-2719)2810965
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 12
|6 P:(DE-2719)2810976
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-351
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Brain Function
|x 0
914 1 _ |y 2021
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2021-01-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2021-01-29
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2021-01-29
915 _ _ |a National-Konsortium
|0 StatID:(DE-HGF)0430
|2 StatID
|d 2022-11-08
|w ger
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1060
|2 StatID
|b Current Contents - Agriculture, Biology and Environmental Sciences
|d 2022-11-08
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b P NATL ACAD SCI USA : 2021
|d 2022-11-08
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2022-11-08
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2022-11-08
915 _ _ |a IF >= 10
|0 StatID:(DE-HGF)9910
|2 StatID
|b P NATL ACAD SCI USA : 2021
|d 2022-11-08
920 1 _ |0 I:(DE-2719)1011003
|k AG Isbrandt
|l Experimental Neurophysiology
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)1011003
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21