Apr 4, 2017

Top2b is involved in the formation of outer segment and synapse during late-stage photoreceptor differentiation by controlling key genes of photoreceptor transcriptional regulatory network

Journal of Neuroscience Research
Ying LiLi Cai

Abstract

Topoisomerase II beta (Top2b) is an enzyme that alters the topologic states of DNA during transcription. Top2b deletion in early retinal progenitor cells causes severe defects in neural differentiation and affects cell survival in all retinal cell types. However, it is unclear whether the observed severe phenotypes are the result of cell-autonomous/primary defects or non-cell-autonomous/secondary defects caused by alterations of other retinal cells. Using photoreceptor cells as a model, we first characterized the phenotypes in Top2b conditional knockout. Top2b deletion leads to malformation of photoreceptor outer segments (OSs) and synapses accompanied by dramatic cell loss at late-stage photoreceptor differentiation. Then, we performed mosaic analysis with shRNA-mediated Top2b knockdown in neonatal retina using in vivo electroportation to target rod photoreceptors in neonatal retina. Top2b knockdown causes defective OS without causing a dramatic cell loss, suggesting a Top2b cell-autonomous function. Furthermore, RNA-seq analysis reveals that Top2b controls the expression of key genes in the photoreceptor gene-regulatory network (e.g., Crx, Nr2e3, Opn1sw, Vsx2) and retinopathy-related genes (e.g., Abca4, Bbs7, Pde6b). Together...Continue Reading

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References

  • References10
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Citations

Mentioned in this Paper

Photoreceptors
Autonomic Nervous System Disorders
In Vivo
ABCA4 protein, human
Transcriptional Regulation
MRNA Maturation
Gene Knockdown Techniques
Photoreceptor Outer Segment
Entire Retina
Genes

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