PUBLICATION

Her9/Hes4 is required for retinal photoreceptor development, maintenance, and survival

Authors
Coomer, C.E., Wilson, S.G., Titialii-Torres, K.F., Bills, J.D., Krueger, L.A., Petersen, R.A., Turnbaugh, E.M., Janesch, E.L., Morris, A.C.
ID
ZDB-PUB-200711-8
Date
2020
Source
Scientific Reports   10: 11316 (Journal)
Registered Authors
Morris, Ann C., Titialii-Torres, Kayla
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Cell Differentiation
  • Cell Proliferation
  • Neurogenesis*
  • Retinal Cone Photoreceptor Cells/pathology
  • Retinal Cone Photoreceptor Cells/physiology*
  • Retinal Rod Photoreceptor Cells/pathology
  • Retinal Rod Photoreceptor Cells/physiology*
  • Zebrafish/embryology*
  • Zebrafish Proteins/physiology*
PubMed
32647335 Full text @ Sci. Rep.
Abstract
The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormal outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects, her9 mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Müller glia. Mutation of her9 was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes