Journal
NEUROSCIENCE
Volume 411, Issue -, Pages 76-85Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2019.05.024
Keywords
spastin; neural stem cell; brain development; primary cilia; microtubule
Categories
Funding
- KRIBB Initiative Research Program from National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [KGM5221911]
- Brain Research Program from National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2015M3C7A1029113]
- Postgenomic Research Program from National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2014M3C9A2064619]
- National Research Council of Science & Technology (NST), Republic of Korea [KGM5221911] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Spastin is a microtubule-severing enzyme encoded by SPAST, which is broadly expressed in various cell types originated from multiple organs. Even though SPAST is well known as a regulator of the axon growth and arborization in neurons and a genetic factor of hereditary spastic paraplegia, it also takes part in a wide range of other cellular functions including the regulation of cell division and proliferation. In this study, we investigated a novel biological role of spastin in developing brain using Spast deficient mouse embryonic neural stem cells (NSCs) and perinatal mouse brain. We found that the expression of spastin begins at early embryonic stages in mouse brain. Using Spast shRNA treated NSCs and mouse brain, we showed that Spast deficiency leads to decrease of NSC proliferation and neuronal lineage differentiation. Finally, we found that spastin controls NSC proliferation by regulating microtubule dynamics in primary cilia. Collectively, these data demonstrate that spastin controls brain development by the regulation of NSC functions at early developmental stages. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
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