Spastin contributes to neural development through the regulation of microtubule dynamics in the primary cilia of neural stem cells

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Title
Spastin contributes to neural development through the regulation of microtubule dynamics in the primary cilia of neural stem cells
Author(s)
Bohyeon Jeong; Tae Hwan Kim; Dae Soo Kim; W H Shin; Jae-Ran LeeNam-Soon KimDa Yong Lee
Bibliographic Citation
Neuroscience, vol. 411, pp. 76-85
Publication Year
2019
Abstract
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.
Keyword
spastinneural stem cellbrain developmentprimary ciliamicrotubule.
ISSN
0306-4522
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.neuroscience.2019.05.024
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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