Academic journal article Genetics

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

Academic journal article Genetics

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

Article excerpt

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.

Afundamental question in developmental biology is the control of neurogenesis. Proper neural development underlies the basic cellular processes required within all cells of the mature nervous system. Neurophysiology, and even broader processes such as consciousness or intelligence intimately depend upon proper developmental control of cells within the nervous system. The developing eye of the fruit fly Drosophila melanogaster serves as an excellent system to model how neurogenesis is controlled within a developing nervous tissue.TheadultDrosophilaeye consists of~800regularly spaced unit eyes, called ommatidia. Each ommatidium contains 20 cells: 8 photoreceptor neurons (R1-R8) and 12 accessory cells (cone, pigment, and bristle cells) arranged in a stereotypical array (Ready et al. 1976; Hsiung and Moses 2002; Mollereau and Domingos 2005), and each of which requires exquisite precision in their morphology for proper function. This morphological exactness requires precision in development. Development of the eye begins as a monolayer field of undifferentiated columnar epithelial cells (the eye/ antennal imaginal disc). These cells grow by random proliferation until, during the early third instar larval stage, a wave of differentiation, marked by a band of cells with constricted apical actin cytoskeletal rings (the morphogenetic furrow) begins at the posterior margin of the presumptive eye disc and sweeps anteriorly across the eye field. As the furrow moves across the disc, new columns of precisely spaced retinal founder cells (the R8 photoreceptor cell) are specified roughly every 2 hours (Ready et al. 1976; Basler and Hafen 1989; Wolff and Ready 1993). The central event in R8 founder cell specification is the initial expression and eventual refinement of the proneural transcription factor Atonal (Ato) within the developing R8 neuron ( Jarman et al. 1994; White and Jarman 2000).

Ato protein is initially expressed in a broad stripe of cells just anterior to the morphogenetic furrow (Figure 1A) ( Jarman et al. 1994). At the leading edge of the furrow, Ato expression is refined to small clusters of ~20 cells, the "intermediate groups" (arrows in Figure 1B) ( Jarman et al. 1995). Later, within the furrow, Ato expression is refined to single cells, the future R8 photoreceptor cells (arrowheads in Figure 1B) ( Jarman et al. 1995; Baker et al. 1996). Ato expression is eventually lost in these founder cells as the furrow advances more anteriorly, although the R8 cell fate is maintained through the expression of Senseless within the R8 (Frankfort et al. …

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