Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.

Details

Serval ID
serval:BIB_6AB4448DA6E1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.
Journal
Cell
Author(s)
Fiddes I.T., Lodewijk G.A., Mooring M., Bosworth C.M., Ewing A.D., Mantalas G.L., Novak A.M., van den Bout A., Bishara A., Rosenkrantz J.L., Lorig-Roach R., Field A.R., Haeussler M., Russo L., Bhaduri A., Nowakowski T.J., Pollen A.A., Dougherty M.L., Nuttle X., Addor M.C., Zwolinski S., Katzman S., Kriegstein A., Eichler E.E., Salama S.R., Jacobs FMJ, Haussler D.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
31/05/2018
Peer-reviewed
Oui
Volume
173
Number
6
Pages
1356-1369.e22
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals that different alleles of NOTCH2NL have varying potencies to enhance Notch signaling by interacting directly with NOTCH receptors. Consistent with a role in Notch signaling, NOTCH2NL ectopic expression delays differentiation of neuronal progenitors, while deletion accelerates differentiation into cortical neurons. Furthermore, NOTCH2NL genes provide the breakpoints in 1q21.1 distal deletion/duplication syndrome, where duplications are associated with macrocephaly and autism and deletions with microcephaly and schizophrenia. Thus, the emergence of human-specific NOTCH2NL genes may have contributed to the rapid evolution of the larger human neocortex, accompanied by loss of genomic stability at the 1q21.1 locus and resulting recurrent neurodevelopmental disorders.
Keywords
Animals, Brain/embryology, Cell Differentiation, Cerebral Cortex/physiology, Embryonic Stem Cells/metabolism, Female, Gene Deletion, Genes, Reporter, Gorilla gorilla, HEK293 Cells, Humans, Neocortex/cytology, Neural Stem Cells/metabolism, Neurogenesis/physiology, Neuroglia/metabolism, Neurons/metabolism, Pan troglodytes, Receptor, Notch2/genetics, Receptor, Notch2/metabolism, Sequence Analysis, RNA, Signal Transduction, 1q21.1, Notch signaling, autism, cortical organoids, human evolution, neural stem cells, neurodevelopment, neurodevelopmental disorders, segmental duplications, structural variation
Pubmed
Web of science
Create date
15/06/2018 17:05
Last modification date
20/08/2019 14:25
Usage data