Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells.
Topoisomerase IIbeta is required for proper retinal development and survival of postmitotic cells.
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DOI：
10.1242/bio.20146767
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发表时间：
2014-02-15
期刊：
影响因子：
2.4
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Li Y;Hao H;Tzatzalos E;Lin RK;Doh S;Liu LF;Lyu YL;Cai L
拓扑异构酶II β（Top 2b）是一种通过催化DNA双链体相互通过来调节DNA超螺旋的酶。它在有丝分裂后细胞中广泛表达，并且已知在隔膜中神经肌肉接头的发育和大脑皮层中层状结构的适当形成期间起作用。然而，由于传统的组成型和脑特异性Top 2b基因敲除小鼠的围产期死亡表型，Top 2b的精确体内功能，特别是在出生后的神经发育，仍有待确定。使用组成型和视网膜特异性基因敲除小鼠模型，我们发现Top 2b缺陷导致延迟的神经元分化，网状层和光感受器外段的变性，以及视网膜细胞数量的急剧减少。通过RNA测序进行的全基因组转录组分析显示，参与神经元存活和神经系统发育的基因在Top 2b缺陷型视网膜中优先受到影响。总的来说，我们的研究结果表明Top 2b在视网膜有丝分裂后神经元的正常发育和维持/存活中具有重要功能。
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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影响因子：
6.2
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