2. Academic Validation
  3. Kinesin-5 Eg5 is essential for spindle assembly, chromosome stability and organogenesis in development

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

  • Cell Death Discov. 2022 Dec 13;8(1):490. doi: 10.1038/s41420-022-01281-1.
Wen-Xin Yu # 1 2,  Yu-Kun Li # 1 2,  Meng-Fei Xu # 1 2,  Chen-Jie Xu 1 2,  Jie Chen 1 2,  Ya-Lan Wei 3 4,  Zhen-Yu She 5 6
Affiliations

Affiliations

  • 1 Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, 350122, Fuzhou, Fujian, China.
  • 2 Key Laboratory of Stem Cell Engineering and Regenerative Medicine, Fujian Province University, 350122, Fuzhou, Fujian, China.
  • 3 Medical Research Center, Fujian Maternity and Child Health Hospital, 350001, Fuzhou, Fujian, China.
  • 4 College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 350122, Fuzhou, Fujian, China.
  • 5 Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, 350122, Fuzhou, Fujian, China. zhenyushe@fjmu.edu.cn.
  • 6 Key Laboratory of Stem Cell Engineering and Regenerative Medicine, Fujian Province University, 350122, Fuzhou, Fujian, China. zhenyushe@fjmu.edu.cn.
  • # Contributed equally.
PMID: 36513626 DOI: 10.1038/s41420-022-01281-1
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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