PUBLICATION

Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development

Authors
Yu, W.X., Li, Y.K., Xu, M.F., Xu, C.J., Chen, J., Wei, Y.L., She, Z.Y.
ID
ZDB-PUB-221216-6
Date
2022
Source
Cell death discovery   8: 490490 (Journal)
Registered Authors
Keywords
none
MeSH Terms
none
PubMed
36513626 Full text @ Cell Death Discov
Abstract
Chromosome stability relies on bipolar spindle assembly and faithful chromosome segregation during cell division. Kinesin-5 Eg5 is a plus-end-directed kinesin motor protein, which is essential for spindle pole separation and chromosome alignment in mitosis. Heterozygous Eg5 mutations cause autosomal-dominant microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome in humans. However, the developmental roles and cellular mechanisms of Eg5 in organogenesis remain largely unknown. In this study, we have shown that Eg5 inhibition leads to the formation of the monopolar spindle, chromosome misalignment, polyploidy, and subsequent apoptosis. Strikingly, long-term inhibition of Eg5 stimulates the immune responses and the accumulation of lymphocytes in the mouse spleen through the innate and specific immunity pathways. Eg5 inhibition results in metaphase arrest and cell growth inhibition, and suppresses the formation of somite and retinal development in zebrafish embryos. Our data have revealed the essential roles of kinesin-5 Eg5 involved in cell proliferation, chromosome stability, and organogenesis during development. Our findings shed a light on the cellular basis and pathogenesis in microcephaly, primary lymphedema, and chorioretinal dysplasia syndrome of Eg5-mutation-positive patients.
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Human Disease / Model
Sequence Targeting Reagents
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