PUBLICATION
Transcription factors underlying photoreceptor diversity
- Authors
- Angueyra, J.M., Kunze, V.P., Patak, L.K., Kim, H., Kindt, K., Li, W.
- ID
- ZDB-PUB-230207-22
- Date
- 2023
- Source
- eLIFE 12: (Journal)
- Registered Authors
- Kindt, Katie
- Keywords
- cone subtypes, developmental biology, neuroscience, photoreceptor fate, retina, transcription factor, transcriptomics, zebrafish
- Datasets
- GEO:GSE188560
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Receptors, Cytoplasmic and Nuclear/metabolism
- Retina/metabolism
- Retinal Cone Photoreceptor Cells/physiology
- Transcription Factors*/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36745553 Full text @ Elife
Citation
Angueyra, J.M., Kunze, V.P., Patak, L.K., Kim, H., Kindt, K., Li, W. (2023) Transcription factors underlying photoreceptor diversity. eLIFE. 12:.
Abstract
During development, retinal progenitors navigate a complex landscape of fate decisions to generate the major cell classes necessary for proper vision. Transcriptional regulation is critical to generate diversity within these major cell classes. Here, we aim to provide the resources and techniques required to identify transcription factors necessary to generate and maintain diversity in photoreceptor subtypes, which are critical for vision. First, we generate a key resource: a high-quality and deep transcriptomic profile of each photoreceptor subtype in adult zebrafish. We make this resource openly accessible, easy to explore, and have integrated it with other currently available photoreceptor transcriptomic datasets. Second, using our transcriptomic profiles, we derive an in-depth map of expression of transcription factors in photoreceptors. Third, we use efficient CRISPR-Cas9 based mutagenesis to screen for null phenotypes in F0 larvae (F0 screening) as a fast, efficient, and versatile technique to assess the involvement of candidate transcription factors in the generation of photoreceptor subtypes. We first show that known phenotypes can be easily replicated using this method: loss of S cones in foxq2 mutants and loss of rods in nr2e3 mutants. We then identify novel functions for the transcription factor Tbx2, demonstrating that it plays distinct roles in controlling the generation of all photoreceptor subtypes within the retina. Our study provides a roadmap to discover additional factors involved in this process. Additionally, we explore four transcription factors of unknown function (Skor1a, Sall1a, Lrrfip1a, and Xbp1), and find no evidence for their involvement in the generation of photoreceptor subtypes. This dataset and screening method will be a valuable way to explore the genes involved in many other essential aspects of photoreceptor biology.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping