Drosophila eyes absent is required for normal cone and pigment cell development

PLoS One. 2014 Jul 24;9(7):e102143. doi: 10.1371/journal.pone.0102143. eCollection 2014.

Abstract

In Drosophila, development of the compound eye is orchestrated by a network of highly conserved transcriptional regulators known as the retinal determination (RD) network. The retinal determination gene eyes absent (eya) is expressed in most cells within the developing eye field, from undifferentiated retinal progenitors to photoreceptor cells whose differentiation begins at the morphogenetic furrow (MF). Loss of eya expression leads to an early block in retinal development, making it impossible to study the role of eya expression during later steps of retinal differentiation. We have identified two new regulatory regions that control eya expression during retinal development. These two enhancers are necessary to maintain eya expression anterior to the MF (eya-IAM) and in photoreceptors (eya-PSE), respectively. We find that deleting these enhancers affects developmental events anterior to the MF as well as retinal differentiation posterior to the MF. In line with previous results, we find that reducing eya expression anterior to the MF affects several early steps during early retinal differentiation, including cell cycle arrest and expression of the proneural gene ato. Consistent with previous observations that suggest a role for eya in cell proliferation during early development we find that deletion of eya-IAM leads to a marked reduction in the size of the adult retinal field. On the other hand, deletion of eya-PSE leads to defects in cone and pigment cell development. In addition we find that eya expression is necessary to activate expression of the cone cell marker Cut and to regulate levels of the Hedgehog pathway effector Ci. In summary, our study uncovers novel aspects of eya-mediated regulation of eye development. The genetic tools generated in this study will allow for a detailed study of how the RD network regulates key steps in eye formation.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Cycle Checkpoints / genetics
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Enhancer Elements, Genetic*
  • Eye Proteins / genetics*
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Larva / genetics
  • Larva / growth & development
  • Larva / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organogenesis / genetics
  • Retinal Cone Photoreceptor Cells / cytology
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Retinal Pigment Epithelium / growth & development
  • Retinal Pigment Epithelium / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Transcription Factors
  • ato protein, Drosophila
  • ci protein, Drosophila
  • ct protein, Drosophila
  • eya protein, Drosophila