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Sci Rep. 2017 Dec 11;7(1):17308. doi: 10.1038/s41598-017-15253-4.

Eml1 loss impairs apical progenitor spindle length and soma shape in the developing cerebral cortex.

Author information

1
INSERM UMR-S 839, 17 rue du Fer à Moulin, Paris, 75005, France.
2
Sorbonne Universités, Université Pierre et Marie Curie, 4 Place Jussieu, Paris, 75005, France.
3
Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris, 75005, France.
4
Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA.
5
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
6
Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
7
Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, 26 rue d'Ulm, 75248 Cedex 05, Paris, France.
8
Institut Jacques Monod, UMR7592 CNRS, Paris, France.
9
Department of Biochemistry, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester, LE1 9HN, UK.
10
Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 21 rue du Bugnon, 1011, Lausanne, Switzerland.
11
Department of Fundamental Neurosciences, University of Lausanne, 1005, Lausanne, Switzerland.
12
Structural Motility, Institut Curie, Centre de Recherche; CNRS, UMR144, 26 rue d'Ulm, Cedex 05, Paris, 75248, France.
13
INSERM UMR-S 839, 17 rue du Fer à Moulin, Paris, 75005, France. fiona.francis@inserm.fr.
14
Sorbonne Universités, Université Pierre et Marie Curie, 4 Place Jussieu, Paris, 75005, France. fiona.francis@inserm.fr.
15
Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris, 75005, France. fiona.francis@inserm.fr.

Abstract

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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