期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-15253-4
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资金
- French Agence National de la Recherche [ANR-13-BSV4-0008-01]
- Inserm
- CNRS
- UPMC
- Fondation Bettencourt Schueller
- Federation pour la Recherche sur le cerveau (FRC)
- European Union [60253]
- JTC Neurodevelopmental Disorders
- ANR [NEURON8-Full-815-006 STEM-MCD]
- French Ministry of Research
- Fondation pour la Recherche Medicale
- Ecole des Neurosciences de Paris
- Company of Biologists
- Agence Nationale de la Recherche (ANR) [ANR-13-BSV4-0008] Funding Source: Agence Nationale de la Recherche (ANR)
The ventricular zone (VZ) of the developing cerebral cortex is a pseudostratified epithelium that contains progenitors undergoing precisely regulated divisions at its most apical side, the ventricular lining (VL). Mitotic perturbations can contribute to pathological mechanisms leading to cortical malformations. The HeCo mutant mouse exhibits subcortical band heterotopia (SBH), likely to be initiated by progenitor delamination from the VZ early during corticogenesis. The causes for this are however, currently unknown. Eml1, a microtubule (MT)-associated protein of the EMAP family, is impaired in these mice. We first show that MT dynamics are perturbed in mutant progenitor cells in vitro. These may influence interphase and mitotic MT mechanisms and indeed, centrosome and primary cilia were altered and spindles were found to be abnormally long in HeCo progenitors. Consistently, MT and spindle length regulators were identified in EML1 pulldowns from embryonic brain extracts. Finally, we found that mitotic cell shape is also abnormal in the mutant VZ. These previously unidentified VZ characteristics suggest altered cell constraints which may contribute to cell delamination.
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