Mutations in the Heterotopia Gene Eml1/EML1 Severely Disrupt the Formation of Primary Cilia
| Autor: | Uzquiano, A, Cifuentes-Diaz, C, Jabali, A, Romero, DM, Houllier, A, Dingli, F, Maillard, C, Boland, A, Deleuze, JF, Loew, D, Verheijen - Mancini, Grazia, Bahi-Buisson, N, Ladewig, J, Francis, F |
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| Přispěvatelé: | Institut du Fer à Moulin, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Universität Heidelberg [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Heidelberg University, Gestionnaire, Hal Sorbonne Université, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cortex development and pathology (U1270), Universität Heidelberg [Heidelberg] = Heidelberg University, ANR-16-CE16-0011,DYNEINOPATHY,Mecanismes moléculaires et cellulaires des dyneinopathies(2016), Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
induced pluripotent stem cell Adolescent [SDV]Life Sciences [q-bio] radial glia Classical Lissencephalies and Subcortical Band Heterotopias Mice ventricular zone Pregnancy Animals Humans cortical development Cilia Cells Cultured Adaptor Proteins Signal Transducing cortical malformation progenitor [SDV] Life Sciences [q-bio] HEK293 Cells Mutation Golgi apparatus subcortical heterotopia Female Microtubule-Associated Proteins primary cilium microtubule |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2019, 28 (6), pp.1596-1611.e10. ⟨10.1016/j.celrep.2019.06.096⟩ Cell Reports, 2019, 28 (6), pp.1596-1611.e10. ⟨10.1016/j.celrep.2019.06.096⟩ Cell Reports, 28(6), 1596-+. Cell Press |
| ISSN: | 2211-1247 |
| Popis: | International audience; Apical radial glia (aRGs) are predominant progenitors during corticogenesis. Perturbing their function leads to cortical malformations, including subcortical heterotopia (SH), characterized by the presence of neurons below the cortex. EML1/Eml1 mutations lead to SH in patients, as well as to heterotopic cortex (HeCo) mutant mice. In HeCo mice, some aRGs are abnormally positioned away from the ventricular zone (VZ). Thus, unraveling EML1/Eml1 function will clarify mechanisms maintaining aRGs in the VZ. We pinpoint an unknown EML1/Eml1 function in primary cilium formation. In HeCo aRGs, cilia are shorter, less numerous, and often found aberrantly oriented within vesicles. Patient fibroblasts and human cortical progenitors show similar defects. EML1 interacts with RPGRIP1L, a ciliary protein, and RPGRIP1L mutations were revealed in a heterotopia patient. We also identify Golgi apparatus abnormalities in EML1/Eml1 mutant cells, potentially upstream of the cilia phenotype. We thus reveal primary cilia mechanisms impacting aRG dynamics in physiological and pathological conditions. |
| Databáze: | OpenAIRE |
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