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mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis
Abstract : Radial glial cells (RCGs) are self-renewing progenitor cells that give rise to neurons and glia during embryonic development. Throughout neurogenesis, these cells contact the cerebral ventricles and bear a primary cilium. Although the role of the primary cilium in embryonic patterning has been studied, its role in brain ventricular morphogenesis is poorly characterized. Using conditional mutants, we show that the primary cilia of radial glia determine the size of the surface of their ventricular apical domain through regulation of the mTORC1 pathway. In cilium-less mutants, the orientation of the mitotic spindle in radial glia is also significantly perturbed and associated with an increased number of basal progenitors. The enlarged apical domain of RGCs leads to dilatation of the brain ventricles during late embryonic stages (ventriculomegaly), which initiates hydrocephalus during postnatal stages. These phenotypes can all be significantly rescued by treatment with the mTORC1 inhibitor rapamycin. These results suggest that primary cilia regulate ventricle morphogenesis by acting as a brake on the mTORC1 pathway. This opens new avenues for the diagnosis and treatment of hydrocephalus.
https://hal-ens.archives-ouvertes.fr/hal-02425387
Contributeur : Mathieu Bahin Connectez-vous pour contacter le contributeur
Soumis le : lundi 30 décembre 2019 - 14:07:43
Dernière modification le : vendredi 30 juillet 2021 - 15:42:01
Contributeur : Mathieu Bahin Connectez-vous pour contacter le contributeur
Soumis le : lundi 30 décembre 2019 - 14:07:43
Dernière modification le : vendredi 30 juillet 2021 - 15:42:01
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