Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human - Evolution Paris Seine
Journal Articles Nature Neuroscience Year : 2014

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

Karine Poirier
  • Function : Author
Robert Olaso
Anne-Gaëlle Le Moing
Patrick Berquin
Jean-François Deleuze
  • Function : Author
  • PersonId : 1015006
Jamel Chelly
  • Function : Author
Fiona Francis

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. Emil 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.
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Dates and versions

hal-01514452 , version 1 (18-06-2024)

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Michel Kielar, Francoise Phan Dinh Tuy, Sara Bizzotto, Cécile Lebrand, Camino De Juan Romero, et al.. Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human. Nature Neuroscience, 2014, 17 (7), pp.923-933. ⟨10.1038/nn.3729⟩. ⟨hal-01514452⟩
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