Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events.
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.
McDonald
Elizabeth C
EC
Molecular and Developmental Biology Graduate Program, Division of Developmental Biology and Department of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, USA.
Xie
Baotong
B
Workman
Michael
M
Charlton-Perkins
Mark
M
Terrell
David A
DA
Reischl
Joachim
J
Wimmer
Ernst A
EA
Gebelein
Brian A
BA
Cook
Tiffany A
TA
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C093053:oc protein, Drosophila; D012243:Rhodopsin