UC San Diego

In this dissertation, I study the body shape control mechanism(s) in fruit fly, Drosophila melanogaster. The study focuses on two dominant mutations, namely TweedleD1 and Tubby1, which result in short, thickset body shape in post-embryonic stages. The results of this study are presented in five sections, to report: 1. identification of TweedleD1 gene and Tubby1 gene; 2. functional analysis of the Tweedle family proteins; 3. close examination of TweedleD1 mutants; 4. model of body shape regulation mediated by Tweedle genes; 5. functional, biochemical and regulatory studies of Tweedle family proteins for further investigation. By combining p element-induced male recombination and direct genomic sequencing, genes that are mutated in TweedleD1 (TwdlD1) and Tubby1 (Tb1) mutants were identified, and they were further verified in transgenic flies. Both TwdlD and Tb proteins belong to a novel insect-specific protein family - the Tweedle family. The Tweedle genes encode proteins that are secreted by ectodermal tissues including epidermis, foregut and trachea. Some of these proteins were shown to contribute to extracellular matrix structure - cuticle. Each Tweedle gene has a specific temporal and spatial expression and localization pattern. These patterns of Tweedle genes might be crucial in determining body shape, as suggested by mis-localization of TwdlD1 protein in TwdlD1 mutants. Based on these observations, a model was proposed to consolidate both the large number of Tweedle genes existing in Drosophila genome and the roles of Tweedle proteins in controlling body shape. Lastly, three aspects of Tweedle family were targeted in pilot studies, and preliminary data support promising research directions that could lead to better understanding of this family and their roles in body shape regulation. This demonstration that mutation of Tweedle proteins results in body shape change highlights the role of exoskeleton in determining overall body shape. Similar phenotypes were observed in nematode C. elegans when cuticular collagens were mutated. This recurring scheme of exoskeleton controlling body shape is a result of convergent evolution