Temporal and Isoform-Specific Expression of CTBP2 Is Evolutionarily Conserved Between the Developing Chick and Human Retina

Abstract

Complex transcriptional gene regulation allows for multifaceted isoform production during retinogenesis, and novel isoforms transcribed from a single locus can have unlimited potential to code for diverse proteins with different functions. In this study, we explored the CTBP2/RIBEYE gene locus and its unique repertoire of transcripts that are conserved among vertebrates. We studied the transcriptional coregulator (CTBP2) and ribbon synapse-specific structural protein (RIBEYE) in the chicken retina by performing comprehensive histochemical and sequencing analyses to pinpoint cell and developmental stage-specific expression of CTBP2/RIBEYE in the developing chicken retina. We demonstrated that CTBP2 is widely expressed in retinal progenitors beginning in early retinogenesis but becomes limited to GABAergic amacrine cells in the mature retina. Inversely, RIBEYE is initially epigenetically silenced in progenitors and later expressed in photoreceptor and bipolar cells where they localize to ribbon synapses. Finally, we compared CTBP2/RIBEYE regulation in the developing human retina using a pluripotent stem cell derived retinal organoid culture system. These analyses demonstrate that similar regulation of the CTBP2/RIBEYE locus during chick and human retinal development is regulated by different members of the K50 homeodomain transcription factor family.

Transcriptome dataset of Caenorhabditis elegans responses to varied microbial pathogens

“…Also, poly dT priming often introduces a 3’ bias for transcript characterization, particularly for long messages. Lastly, though the quantity of our reads depth in this study is below the threshold for rare isoform identification, there are enough reads per sample in our study to characterize abundant alternative mRNA isoforms as previously demonstrated [19] . Taking these considerations into account, these data will be a useful resource for the C. elegans community and others, providing a robust and accurate analysis of the polyadenylated transcriptional networks in nematodes exposed to varied bacterial pathogens.…”

Bulk RNA sequencing analysis of developing human induced pluripotent cell-derived retinal organoids

“…A human induced pluripotent stem cell (hiPSC)-derived 3D retinal organoid system that mimics fetal human retinal development was used as previously described with authorization from the UC San Diego Institutional Review Board Committee 9 , 12 , 20 . The IMR90.4 iPSC line was obtained from WiCell (Madison, WI).…”

“…Furthermore, the data can be applied to compare gene regulation across species. For instance, we compared mRNA transcripts derived from embryonic chicken retinas to the RNA-seq reads from the current study and highlighted the conserved nature of transcriptional regulation of CTBP2/RIBEYE 20 . A recent report by Wahlin et al .…”

A Novel Cre Recombinase Mouse Strain for Cell-Specific Deletion of Floxed Genes in Ribbon Synapse-Forming Retinal Neurons

“…The RIBEYE/CtBP2 gene is a bi-functional gene and generates two gene products [18]. The CtBP2 promotor drives ubiquitous CtBP2 expression in most eukaryotic cells [18][19][20][21], whereas the RIBEYE promotor drives RIBEYE expression only in ribbon synapse-forming cells [12,[22][23][24][25].…”