期刊
DEVELOPMENTAL BIOLOGY
卷 347, 期 1, 页码 122-132出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2010.08.016
关键词
Orthodenticle; Crx; Otx tail; Retinogenesis; Cell-specific gene expression; Photoreceptors
资金
- Ohio Preventing Blindness
- NIH [T32 HD046387, R01-EY017907]
- Boehringer Ingelheim
- German Research Foundation (DFG) [Wi 1797/2-2]
- Cincinnati Children's Research Foundation
- Research Preventing Blindness
- E. Matilda Ziegler Foundation for the Blind
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. (c) 2010 Elsevier Inc. All rights reserved.
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