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

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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Kielar M,Tuy FP,Bizzotto S,Lebrand C,de Juan Romero C,Poirier K,Oegema R,Mancini GM,Bahi-Buisson N,Olaso R,Le Moing AG,Boutourlinsky K,Boucher D,Carpentier W,Berquin P,Deleuze JF,Belvindrah R,Borrell V,Welker E,Chel

doi

10.1038/nn.3729

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

923-33

issue

7

eissn

1097-6256

issn

1546-1726

pii

nn.3729

journal_volume

17

pub_type

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