The role of egr1 in early zebrafish retinogenesis

PLoS One. 2013;8(2):e56108. doi: 10.1371/journal.pone.0056108. Epub 2013 Feb 6.

Abstract

Proper retinal cell differentiation is essential for establishing a functional retina. The purpose of this study is to investigate the role of early growth response 1 (egr1), a transcription factor (TF) that has been reported to control eye development and function, on retinal differentiation in zebrafish. Specifically, cellular changes in the Egr1-knockdown retinas were characterized by immunohistochemistry at 72 and 120 hours post-fertilization (hpf). The results indicate that Egr1 knockdown specifically suppressed the differentiation of subtypes of amacrine cells (ACs) and horizontal cells (HCs), including Parvalbumin- and GABA-positive ACs as well as Islet1-positive HCs. In addition, the knockdown induced a general delay of development of the other retinal cell types. These differentiation problems, particularly the ones with the ACs and HCs, also compromised the integrity of the inner and outer plexiform layers. In the Egr1-knockdown retinas, the expression of ptf1a, a TF that controls the specification of ACs and HCs, was prolonged and found in ectopic locations in the retina up to 72 hpf. Then, it became restricted to the proliferative marginal zone as in the control retinas at 120 hpf. This abnormal and prolonged expression of ptf1a during retinogenesis might affect the differentiation of ACs and HCs in the Egr1-knockdown retinas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / cytology*
  • Amacrine Cells / metabolism
  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Cell Differentiation
  • Early Growth Response Protein 1 / antagonists & inhibitors
  • Early Growth Response Protein 1 / genetics*
  • Early Growth Response Protein 1 / metabolism
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / metabolism
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Morpholinos / pharmacology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retina / embryology*
  • Retina / metabolism
  • Retina / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish / genetics*
  • Zebrafish / metabolism

Substances

  • Early Growth Response Protein 1
  • Morpholinos
  • RNA, Messenger

Grant support

This study was supported by a Pediatric Ophthalmology Research Grant from the Knights Templar Eye Foundation and a Charles D. Kelman, M.D. Scholar award from the International Retinal Research Foundation to LZ, a Sigma Xi Grant-in-Aid award for vision-related research to DP, and awards from Hope for Vision & Showalter Research Trust to YFL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.