期刊
CELL REPORTS
卷 28, 期 6, 页码 1596-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.06.096
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资金
- Region Ile de France
- FRC Rotary
- Inserm
- Centre National de la Recherche Scientifique (CNRS)
- Sorbonne University
- French Agence National de la Recherche [ANR-13-BSV4-0008-01, ANR-16-CE16-0011-03]
- Fondation Bettencourt Schueller
- European Union (EU-HEALTH-2013, DESIRE) [60253]
- ERA-Net NEURON JTC 2015 Neurodevelopmental Disorders program
- ANR [NEURON8-Full-815-006 STEM-MCD]
- Fondation Maladies Rares/Phenomin [IR4995]
- European Cooperation in Science and Technology (COST Action) [CA16118]
- Hector Foundation II
- French ANR under E-Rare-3, the ERA-Net for Research on Rare Diseases [ERARE18-049]
- Fondation de France (Prix Valerie Chamaillard, Fondation Francaise pour la Recherche sur l'Epilepsie)
- Region Ile-de-France [2013-2-EML-02-ICR-1]
- Fondation pour la Recherche Medicale [DGE20121125630]
- ENP PhD grant
- Company of Biologists
- Agence Nationale de la Recherche (ANR) [ANR-13-BSV4-0008, ANR-16-CE16-0011] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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