Novel targets of BMP/DPP signaling during Drosophila wing disc development
Milan Szuperak
The BMP signaling pathway plays a key role in controlling growth and epithelial morphogenesis during development of the Drosophila wing disc. The BMP homolog Decapentaplegic (DPP) forms a morphogen gradient orthogonal to the tissue A/P axis, establishing distinct territories of differential gene expression. At the present time, all of the known DPP target genes are transcription factors and the DPP/BMP effector molecules that ultimately regulate proliferation and morphogenesis remain unknown. To identify such genes, we performed a microarray screen, comparing DPP-deprived epithelial cells to wild type controls. This approach identified novel genes showing specific expression pattern in the wing imaginal disc. Presently, we are analyzing the candidate genes using molecular, genetic, biochemical, and imaging techniques. One particularly promising candidate appears to be a direct (threshold-independent) transcriptional target of DPP/BMP signaling.
Studying the role of SUMOylation in the development of Drosophila imaginal discs.
Kiki Kanakousaki
Animal development requires not only transcription and translation of thousands of important regulatory molecules, but also their modification by post-translational mechanisms such as phosphorylation, proteolytic cleavage, or ubiquitination. SUMOylation is a post-translational protein modification proposed to impact on many cellular processes, although the role of SUMOylation at the organismal level and in broad processes like development is not well understood. In a genetic screen we found a novel mutation in a key component of the biochemical pathway of SUMO conjugation. This mutation dramatically affected the growth of imaginal discs, although many other larval structures were unperturbed. Using genetics, biochemistry, cytometry and imaging, we analyzed the phenotype and found that mutants cells exhibit reduced levels of SUMOylation and defects in mitosis. Our goal is to understand the pathways and proteins affected by SUMOylation, leading to the observed phenotype.
Novel mutations affecting appendage growth and body size in Drosophila melanogaster
Sally Salah
Most organisms grow and develop into a preset size and shape. One of our objectives is to understand the underlying mechanisms that are responsible for organismal growth control. In order to identify these mechanisms, we are studying mutations in two novel genes. The mutation of the first gene specifically affects wing disc growth, and mutation of the second results in a dramatic reduction in overall body size. We are using classical molecular-genetic approaches to identify the genes responsible for these two distinct growth defects.