Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events

Elizabeth C. McDonald, Baotong Xie, Michael Workman, Mark Charlton-Perkins, David A. Terrell, Joachim Reischl, Ernst A. Wimmer, Brian A. Gebelein, Tiffany A. Cook

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Orthodenticle (Otd)-related transcription factors are essential for anterior patterning and brain morphogenesis from Cnidaria to Mammals, and genetically underlie several human retinal pathologies. Despite their key developmental functions, relatively little is known regarding the molecular basis of how these factors regulate downstream effectors in a cell- or tissue-specific manner. Many invertebrate and vertebrate species encode two to three Otd proteins, whereas Drosophila encodes a single Otd protein. In the fly retina, Otd controls rhabdomere morphogenesis of all photoreceptors and regulates distinct Rhodopsin-encoding genes in a photoreceptor subtype-specific manner. Here, we performed a structure-function analysis of Otd during Drosophila eye development using in vivo rescue experiments and in vitro transcriptional regulatory assays. Our findings indicate that Otd requires at least three distinct transcriptional regulatory domains to control photoreceptor-specific rhodopsin gene expression and photoreceptor morphogenesis. Our results also uncover a previously unknown role for Otd in preventing co-expression of sensory receptors in blue vs. green-sensitive R8 photoreceptors. Sequence analysis indicates that many of the transcriptional regulatory domains identified here are conserved in multiple Diptera Otd-related proteins. Thus, these studies provide a basis for identifying shared molecular pathways involved in a wide range of developmental processes.

Original languageEnglish (US)
Pages (from-to)122-132
Number of pages11
JournalDevelopmental Biology
Volume347
Issue number1
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Keywords

  • Cell-specific gene expression
  • Crx
  • Orthodenticle
  • Otx tail
  • Photoreceptors
  • Retinogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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