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J.R. Curtiss, M. Mlodzik; Distal Antenna and Distal Antenna–related, Two Nuclear Proteins Containing Pipsqueak Motifs, Induce Ectopic Eyes and Are Required for Eye Development in Drosophila melanogaster . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3123.
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Purpose: The distal antenna (dan) and distal antenna–related (danr) genes encode novel nuclear proteins that contain a potential DNA–binding domain called a pipsqueak motif, which is found in many proteins that regulate chromatin structure. This study was conducted to investigate a possible role for dan and danr in eye specification in Drosophila melanogaster, and to determine their relationships to other specification factors including Eyeless/Pax–6, Eyes absent, Sine oculis (a homologue of the vertebrate Six genes), and Dachshund. Methods: Expression of Dan and Danr during Drosophila eye development was examined. Loss– and gain– of function dan and danr mutant eye phenotypes were characterized. Both genetic and molecular tools were used to analyze the relationships among dan, danr and other specification factors. Results: Misexpression of dan or danr in antennal precursors leads to ectopic Ey/Pax–6 expression and ectopic eye formation. Single and double loss–of–function dan and danr mutants have small, rough eyes. Dan and Danr are involved in several aspects of eye development, including the induction and spacing of the founding ommatidial cell, and the subsequent recruitment and differentiation of additional photoreceptors in each ommatidium. In addition, Dan and Danr participate in the regulatory loops that control expression of the Eyeless/Pax6, Eyes absent, Sine oculis, and Dachshund eye specification factors. Conclusions: Dan and Danr are required and sufficient for Drosophila eye specification. They participate in the early eye gene regulatory loops that contribute to specificity in eye development. The pleiotropic and relatively weak phenotypes of dan and danr mutants suggest they play permissive rather than instructive roles in eye development. Since Dan and Danr contain a motif associated with chromatin structure regulation, they are likely to be involved in initiating or maintaining a chromatin structure conducive to the subsequent actions of transcription factors that promote eye differentiation.
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