Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
Autor: | Yi Lisa Lyu Lyu, Ying Li, Evangeline Tzatzalos, Leroy-Fong Liu, Ren Kuo Lin, Li Cai, Hailing Hao, Sung Tae Doh |
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Rok vydání: | 2014 |
Předmět: |
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 |
Zdroj: | Biology Open, Vol 3, Iss 2, Pp 172-184 (2014) Biology Open |
ISSN: | 2046-6390 |
DOI: | 10.1242/bio.20146767 |
Popis: | 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. |
Databáze: | OpenAIRE |
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