OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification

eLife

Diana Y Kim¹  Diego F Buenaventura²  Miruna Georgiana Ghinia Tegla²  Kevin C Gonzalez²  Cassandra Thakurdin²  Mark M Emerson² 

[1] PhD Program in Biology, The Graduate Center of the City University of New York (CUNY), New York, United States;Department of Biology, The City College of New York, City University of New York (CUNY), New York, United States;

关键词: photoreceptors;    cell fate;    gene regulatory network;    retinal progenitor cell;    single cell profiling;    gene editing;   

DOI  :  10.7554/eLife.54279

来源: DOAJ

【 摘 要 】

During vertebrate retinal development, subsets of progenitor cells generate progeny in a non-stochastic manner, suggesting that these decisions are tightly regulated. However, the gene-regulatory network components that are functionally important in these progenitor cells are largely unknown. Here we identify a functional role for the OTX2 transcription factor in this process. CRISPR/Cas9 gene editing was used to produce somatic mutations of OTX2 in the chick retina and identified similar phenotypes to those observed in human patients. Single cell RNA sequencing was used to determine the functional consequences OTX2 gene editing on the population of cells derived from OTX2-expressing retinal progenitor cells. This confirmed that OTX2 is required for the generation of photoreceptors, but also for repression of specific retinal fates and alternative gene regulatory networks. These include specific subtypes of retinal ganglion and horizontal cells, suggesting that in this context, OTX2 functions to repress sister cell fate choices.

【 授权许可】

Unknown