Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_2B2CFDAC2327
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.
Journal
Nature Neuroscience
Author(s)
Kielar M., Tuy F.P., Bizzotto S., Lebrand C., de Juan Romero C., Poirier K., Oegema R., Mancini G.M., Bahi-Buisson N., Olaso R., Le Moing A.G., Boutourlinsky K., Boucher D., Carpentier W., Berquin P., Deleuze J.F., Belvindrah R., Borrell V., Welker E., Chelly J., Croquelois A., Francis F.
ISSN
1546-1726 (Electronic)
ISSN-L
1097-6256
Publication state
Published
Issued date
2014
Volume
17
Number
7
Pages
923-933
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen HeCo mice display this phenotype, and our study revealed that misplaced apical progenitors contribute to heterotopia formation. While HeCo neurons migrated at the same speed as wild type, abnormally distributed dividing progenitors were found throughout the cortical wall from embryonic day 13. We identified Eml1, encoding a microtubule-associated protein, as the gene mutated in HeCo mice. Full-length transcripts were lacking as a result of a retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo progenitor phenotype and reexpression rescued it. We further found EML1 to be mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human.
Pubmed
Web of science
Open Access
Yes
Create date
27/07/2014 15:02
Last modification date
20/08/2019 13:10
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