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

Ying Li, Hailing Hao, Evangeline Tzatzalos, Ren Kuo Lin, Sungtae Doh, Leroy F. Liu, Yi Lisa Lyu Lyu, Li Cai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)172-184
Number of pages13
JournalBiology Open
Volume3
Issue number2
DOIs
StatePublished - Feb 15 2014

Fingerprint

retina
cell viability
Retina
Cell Survival
Cells
Genes
Knockout Mice
DNA
Diaphragms
RNA Sequence Analysis
Neurons
neurodevelopment
Neuromuscular Junction
cerebral cortex
Brain
diaphragm
Gene Expression Profiling
Diaphragm
transcriptomics
photoreceptors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Cell survival
  • Gene regulation
  • Postmitotic cells
  • Retina
  • Retina degeneration
  • Top2b
  • Transcription

Cite this

Li, Ying ; Hao, Hailing ; Tzatzalos, Evangeline ; Lin, Ren Kuo ; Doh, Sungtae ; Liu, Leroy F. ; Lyu, Yi Lisa Lyu ; Cai, Li. / Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells. In: Biology Open. 2014 ; Vol. 3, No. 2. pp. 172-184.
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abstract = "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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Li, Y, Hao, H, Tzatzalos, E, Lin, RK, Doh, S, Liu, LF, Lyu, YLL & Cai, L 2014, 'Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells', Biology Open, vol. 3, no. 2, pp. 172-184. https://doi.org/10.1242/bio.20146767

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 Lyu; Cai, Li.

In: Biology Open, Vol. 3, No. 2, 15.02.2014, p. 172-184.

Research output: Contribution to journalArticle

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AU - Li, Ying

AU - Hao, Hailing

AU - Tzatzalos, Evangeline

AU - Lin, Ren Kuo

AU - Doh, Sungtae

AU - Liu, Leroy F.

AU - Lyu, Yi Lisa Lyu

AU - Cai, Li

PY - 2014/2/15

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N2 - 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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