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首页> 外文期刊>Biology Open >Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells
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Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells

机译：拓扑异构酶IIbeta是适当的视网膜发育和有丝分裂后细胞存活所必需的

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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.
机译：拓扑异构酶IIbeta（Top2b）是一种通过催化DNA双链体相互通过来调节DNA超螺旋的酶。它普遍存在于有丝分裂后的细胞中，并在diaphragm肌神经肌肉接头的发育以及大脑皮层中层状结构的适当形成过程中发挥作用。但是，由于传统的组成型和脑特异性Top2b基因敲除小鼠的围产期死亡表型，Top2b的确切体内功能，尤其是在产后神经发育过程中，尚待确定。使用组成型和视网膜特异性基因敲除小鼠模型，我们显示Top2b缺乏导致神经元分化延迟，网状层变性和感光细胞外节，以及视网膜中细胞数量急剧减少。通过RNA测序进行全基因组转录组分析，发现与神经元存活和神经系统发育有关的基因在Top2b缺陷型视网膜中优先受到影响。总体而言，我们的发现表明Top2b在视网膜的有丝分裂后神经元的正常发育和维持/存活中具有重要作用。

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