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      Identification of Novel Regulators of atonal Expression in the Developing Drosophila Retina

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      Genetics
      Genetics Society of America

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          Abstract

          Atonal is a Drosophila proneural protein required for the proper formation of the R8 photoreceptor cell, the founding photoreceptor cell in the developing retina. Proper expression and refinement of the Atonal protein is essential for the proper formation of the Drosophila adult eye. In vertebrates, expression of transcription factors orthologous to Drosophila Atonal (MATH5/Atoh7, XATH5, and ATH5) and their progressive restriction are also involved in specifying the retinal ganglion cell, the founding neural cell type in the mammalian retina. Thus, identifying factors that are involved in regulating the expression of Atonal during development are important to fully understand how retinal neurogenesis is accomplished. We have performed a chemical mutagenesis screen for autosomal dominant enhancers of a loss-of-function atonal eye phenotype. We report here the identification of five genes required for proper Atonal expression, three of which are novel regulators of Atonal expression in the Drosophila retina. We characterize the role of the daughterless, kismet, and roughened eye genes on atonal transcriptional regulation in the developing retina and show that each gene regulates atonal transcription differently within the context of retinal development. Our results provide additional insights into the regulation of Atonal expression in the developing Drosophila retina.

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          Most cited references67

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          The Hedgehog response network: sensors, switches, and routers.

          The Hedgehog (Hh) signaling pathway is intimately linked to cell growth and differentiation, with normal roles in embryonic pattern formation and adult tissue homeostasis and pathological roles in tumor initiation and growth. Recent advances in our understanding of Hh response have resulted from the identification of new pathway components and new mechanisms of action for old pathway components. The most striking new finding is that signal transmission from membrane to cytoplasm proceeds through recruitment, by the seven-transmembrane protein Smoothened, of an atypical kinesin, which routes pathway activation by interaction with other components of a complex that includes the latent zinc finger transcription factor, Ci.
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            Coordination of growth and cell division in the Drosophila wing.

            In most tissues, cell division is coordinated with increases in mass (i.e., growth). To understand this coordination, we altered rates of division in cell clones or compartments of the Drosophila wing and measured the effects on growth. Constitutive overproduction of the transcriptional regulator dE2F increased expression of the S- and M-phase initiators Cyclin E and String (Cdc25), thereby accelerating cell proliferation. Loss of dE2F or overproduction of its corepressor, RBF, retarded cell proliferation. These manipulations altered cell numbers over a 4- to 5-fold range but had little effect on clone or compartment sizes. Instead, changes in cell division rates were offset by changes in cell size. We infer that dE2F and RBF function specifically in cell cycle control, and that cell cycle acceleration is insufficient to stimulate growth. Variations in dE2F activity could be used to coordinate cell division with growth.
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              Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms

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                Author and article information

                Journal
                Genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                December 15 2008
                December 2008
                December 2008
                October 01 2008
                : 180
                : 4
                : 2095-2110
                Article
                10.1534/genetics.108.093302
                2600944
                18832354
                e15798b8-e6b8-46f7-82bc-6994889e57d9
                © 2008
                History

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