PUBLICATION
Loss-of-function of kinesin-5 KIF11 causes microcephaly, chorioretinopathy, and developmental disorders through chromosome instability and cell cycle arrest
- Authors
- Zhou, Y., Xu, M.F., Chen, J., Zhang, J.L., Wang, X.Y., Huang, M.H., Wei, Y.L., She, Z.Y.
- ID
- ZDB-PUB-240218-13
- Date
- 2024
- Source
- Experimental cell research 436(1): 113975 (Journal)
- Registered Authors
- Keywords
- Chorioretinopathy, Chromosome instability, KIF11, Kinesin, MCLMR, Microcephaly
- MeSH Terms
-
- Retinal Diseases*
- Facies*
- Chromosomal Instability
- Developmental Disabilities
- Phenotype
- Zebrafish/genetics
- Zebrafish/metabolism
- Lymphedema*
- Kinesins/genetics
- Kinesins/metabolism
- Animals
- Microcephaly*/genetics
- Retinal Dysplasia*
- Cell Cycle Checkpoints/genetics
- PubMed
- 38367657 Full text @ Exp. Cell Res.
Citation
Zhou, Y., Xu, M.F., Chen, J., Zhang, J.L., Wang, X.Y., Huang, M.H., Wei, Y.L., She, Z.Y. (2024) Loss-of-function of kinesin-5 KIF11 causes microcephaly, chorioretinopathy, and developmental disorders through chromosome instability and cell cycle arrest. Experimental cell research. 436(1):113975.
Abstract
Kinesin motors play a fundamental role in development by controlling intracellular transport, spindle assembly, and microtubule organization. In humans, patients carrying mutations in KIF11 suffer from an autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR). While mitotic functions of KIF11 proteins have been well documented in centrosome separation and spindle assembly, cellular mechanisms underlying KIF11 dysfunction and MCLMR remain unclear. In this study, we generate KIF11-inhibition chick and zebrafish models and find that KIF11 inhibition results in microcephaly, chorioretinopathy, and severe developmental defects in vivo. Notably, loss-of-function of KIF11 causes the formation of monopolar spindle and chromosome misalignment, which finally contribute to cell cycle arrest, chromosome instability, and cell death. Our results demonstrate that KIF11 is crucial for spindle assembly, chromosome alignment, and cell cycle progression of progenitor stem cells, indicating a potential link between polyploidy and MCLMR. Our data have revealed that KIF11 inhibition cause microcephaly, chorioretinopathy, and development disorders through the formation of monopolar spindle, polyploid, and cell cycle arrest.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping