1. Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
- Author
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Yi Lisa Lyu Lyu, Ying Li, Evangeline Tzatzalos, Leroy-Fong Liu, Ren Kuo Lin, Li Cai, Hailing Hao, and Sung Tae Doh
- Subjects
QH301-705.5 ,Science ,Postmitotic cells ,Biology ,Bioinformatics ,Cell survival ,Retina ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biology (General) ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Retina degeneration ,Phenotype ,Gene regulation ,Cell biology ,medicine.anatomical_structure ,Cerebral cortex ,Knockout mouse ,DNA supercoil ,sense organs ,General Agricultural and Biological Sciences ,Transcription ,Neural development ,Top2b ,030217 neurology & neurosurgery ,Research Article - Abstract
Summary Topoisomerase IIbeta (Top2b) is an enzyme that modulates DNA supercoiling by catalyzing the passage of DNA duplexes through one another. It is ubiquitously expressed in postmitotic cells and known to function during the development of neuromuscular junctions in the diaphragm and the proper formation of laminar structure in the cerebral cortex. However, due to the perinatal death phenotype of the traditional constitutive and brain-specific Top2b knockout mice, the precise in vivo function of Top2b, especially during postnatal neural development, remains to be determined. Using both the constitutive and retina-specific knockout mouse models, we showed that Top2b deficiency resulted in delayed neuronal differentiation, degeneration of the plexiform layers and outer segment of photoreceptors, as well as dramatic reduction in cell number in the retina. Genome-wide transcriptome analysis by RNA sequencing revealed that genes involved in neuronal survival and neural system development were preferentially affected in Top2b-deficient retinas. Collectively, our findings have indicated an important function of Top2b in proper development and the maintenance/survival of postmitotic neurons in the retina.
- Published
- 2014