Onset of atonal expression in Drosophila retinal progenitors involves redundant and synergistic contributions of Ey/Pax6 and So binding sites within two distant enhancers

Dev Biol. 2014 Feb 1;386(1):152-64. doi: 10.1016/j.ydbio.2013.11.012. Epub 2013 Nov 16.

Abstract

Proneural transcription factors drive the generation of specialized neurons during nervous system development, and their dynamic expression pattern is critical to their function. The activation of the proneural gene atonal (ato) in the Drosophila eye disc epithelium represents a critical step in the transition from retinal progenitor cell to developing photoreceptor neuron. We show here that the onset of ato transcription depends on two distant enhancers that function differently in subsets of retinal progenitor cells. A detailed analysis of the crosstalk between these enhancers identifies a critical role for three binding sites for the Retinal Determination factors Eyeless (Ey) and Sine oculis (So). We show how these sites interact to induce ato expression in distinct regions of the eye field and confirm them to be occupied by endogenous Ey and So proteins in vivo. Our study suggests that Ey and So operate differently through the same 3' cis-regulatory sites in distinct populations of retinal progenitors.

Keywords: Atoh7; Eye specification; Math5; Neurogenesis; Proneural factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Binding Sites
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila / embryology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Enhancer Elements, Genetic
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • In Situ Hybridization
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Nervous System / embryology
  • Neurons / metabolism
  • Neurons / physiology
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Retina / embryology*
  • Stem Cells / cytology*
  • Transcription, Genetic

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins
  • So protein, Drosophila
  • ato protein, Drosophila
  • ey protein, Drosophila
  • Green Fluorescent Proteins