Handling Editor: François Guillemot
ABSTRACT
Microtubules (MTs) regulate numerous cellular processes, but their roles in brain morphogenesis are not well known. Here, we show that CAMSAP3, a non-centrosomal microtubule regulator, is important for shaping the lateral ventricles. In differentiating ependymal cells, CAMSAP3 became concentrated at the apical domains, serving to generate MT networks at these sites. Camsap3-mutated mice showed abnormally narrow lateral ventricles, in which excessive stenosis or fusion was induced, leading to a decrease of neural stem cells at the ventricular and subventricular zones. This defect was ascribed at least in part to a failure of neocortical ependymal cells to broaden their apical domain, a process necessary for expanding the ventricular cavities. mTORC1 was required for ependymal cell growth but its activity was downregulated in mutant cells. Lysosomes, which mediate mTORC1 activation, tended to be reduced at the apical regions of the mutant cells, along with disorganized apical MT networks at the corresponding sites. These findings suggest that CAMSAP3 supports mTORC1 signaling required for ependymal cell growth via MT network regulation, and, in turn, shaping of the lateral ventricles.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: T.K., M.T.; Formal analysis: T.K.; Investigation: T.K.; Resources: H.S., M.K.; Writing - original draft: T.K.; Writing - review & editing: T.K., M.T.; Supervision: M.T.; Funding acquisition: M.T.
Funding
This work was supported by the program Grant-in-Aid for Scientific Research (S) (grant number 25221104) from the Japan Society for the Promotion of Science to M.T.
Supplementary information
Supplementary information available online at https://dev.biologists.org/lookup/doi/10.1242/dev.195073.supplemental
- Received July 19, 2020.
- Accepted January 6, 2021.
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