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Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells

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...

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Autores principales: Li, Ying, Hao, Hailing, Tzatzalos, Evangeline, Lin, Ren-Kuo, Doh, Sungtae, Liu, Leroy F., Lyu, Yi Lisa, Cai, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925320/
https://www.ncbi.nlm.nih.gov/pubmed/24463367
http://dx.doi.org/10.1242/bio.20146767
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author Li, Ying
Hao, Hailing
Tzatzalos, Evangeline
Lin, Ren-Kuo
Doh, Sungtae
Liu, Leroy F.
Lyu, Yi Lisa
Cai, Li
author_facet Li, Ying
Hao, Hailing
Tzatzalos, Evangeline
Lin, Ren-Kuo
Doh, Sungtae
Liu, Leroy F.
Lyu, Yi Lisa
Cai, Li
author_sort Li, Ying
collection PubMed
description 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.
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spelling pubmed-39253202014-02-21 Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells Li, Ying Hao, Hailing Tzatzalos, Evangeline Lin, Ren-Kuo Doh, Sungtae Liu, Leroy F. Lyu, Yi Lisa Cai, Li Biol Open Research Article 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. The Company of Biologists 2014-01-17 /pmc/articles/PMC3925320/ /pubmed/24463367 http://dx.doi.org/10.1242/bio.20146767 Text en © 2014. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Li, Ying
Hao, Hailing
Tzatzalos, Evangeline
Lin, Ren-Kuo
Doh, Sungtae
Liu, Leroy F.
Lyu, Yi Lisa
Cai, Li
Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
title Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
title_full Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
title_fullStr Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
title_full_unstemmed Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
title_short Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
title_sort topoisomerase iibeta is required for proper retinal development and survival of postmitotic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925320/
https://www.ncbi.nlm.nih.gov/pubmed/24463367
http://dx.doi.org/10.1242/bio.20146767
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