Abstract
The adult Drosophila melanogaster body develops from imaginal discs, groups of cells set-aside during embryogenesis and expanded in number during larval stages. Specification and development of Drosophila imaginal discs have been studied for many years as models of morphogenesis. These studies are often based on mutations with large developmental effects, mutations that are often lethal in embryos when homozygous. Such forward genetic screens can be limited by factors such as early lethality and genetic redundancy. To identify additional genes and genetic pathways involved in leg imaginal disc development, we employed a Genome Wide Association Study utilizing the natural genetic variation in leg proportionality found in the Drosophila Genetic Reference Panel fly lines. In addition to identifying genes already known to be involved in leg development, we identified several genes involved in pathways that had not previously been linked with leg development. Several of the genes appear to be involved in signaling activities, while others have no known roles at this time. Many of these uncharacterized genes are conserved in mammals, so we can now begin to place these genes into developmental contexts. Interestingly, we identified five genes which, when their function is reduced by RNAi, cause an antenna-to-leg transformation. Our results demonstrate the utility of this approach, integrating the tools of quantitative and molecular genetics to study developmental processes, and provide new insights into the pathways and networks involved in Drosophila leg development.
Highlights
In the fruit fly, Drosophila melanogaster, development of the adult body begins when small clusters of cells are set-aside during embryogenesis to form the imaginal discs [1,2,3,4,5]
Analysis of variance (ANOVA) indicated that there was no significant difference between flies collected in these two methods
genome-wide association study (GWAS) takes advantage of the natural variation in a trait or phenotype to identify genes that contribute to the development of that trait
Summary
Drosophila melanogaster, development of the adult body begins when small clusters of cells are set-aside during embryogenesis to form the imaginal discs [1,2,3,4,5]. Abdominal Hox genes block Dll activation posterior to the thoracic segments [7], while Decapentaplegic (Dpp) and the Epidermal Growth Factor Receptor pathways limit Dll expression dorsally and ventrally, respectively [8]. After the disc primordia are established they receive patterning instructions via a series of signaling molecules, morphogens and transcription factors expressed during the larval stages that establish the proximal-distal (P-D) pattern of the legs (Fig. 1A). On the anterior side of the anterior-posterior border, where Hh signal is strongest, wg and dpp are activated; Dpp is responsible for dorsal fate and Wg for ventral. In the center of the disc where cells experience high levels of both Wg and Dpp, Dll is activated to establish the distal portions of the leg (mid-tibia through tarsus) [10,11,12,13,14]. An alternative model has been suggested proposing different molecular controls activating medial fate [4,18,19]
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