RT Journal Article
SR Electronic
T1 Her9/HES4 is required for retinal photoreceptor development, maintenance, and survival
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 833301
DO 10.1101/833301
A1 Cagney E. Coomer
A1 Stephen G. Wilson
A1 Kayla F. Titialii-Torres
A1 Jessica D. Bills
A1 Laura A. Krueger
A1 Rebecca A. Petersen
A1 Evelyn M. Turnbaugh
A1 Eden L. Janesch
A1 Ann C. Morris
YR 2019
UL http://biorxiv.org/content/early/2019/11/07/833301.abstract
AB 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 mammalian HES4, is a basic helix-loop-helix-orange (bHLH-O) 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 abnormally truncated 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.