Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development.
Wen-Xin YuYu-Kun LiMeng-Fei XuChen-Jie XuJie ChenYa-Lan WeiZhen-Yu ShePublished in: Cell death discovery (2022)
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.
Keyphrases
- dna methylation
- copy number
- genome wide
- immune response
- cell proliferation
- zika virus
- single cell
- intellectual disability
- cell cycle
- newly diagnosed
- oxidative stress
- end stage renal disease
- ejection fraction
- stem cells
- case report
- toll like receptor
- signaling pathway
- bipolar disorder
- prognostic factors
- cell therapy
- mass spectrometry
- autism spectrum disorder
- bone marrow
- peripheral blood
- binding protein
- artificial intelligence