Regulation of final organ size is a complex developmental process involving the integration of systemic, organ-specific and environmentally regulated processes. Together these processes enable co-ordination of organ growth with body growth and the achievement of correct organ size. Dysregulation in these processes causes over- or under growth of organs resulting in compromised organ function. Understanding the mechanisms contributing to regulation of organ size is therefore key to understanding organ function. My research has focused on understanding two distinct aspects of developmental growth control. Firstly, what role does systemic hormonal signaling play in regulating final organ size? Second, what is the role of transcriptional regulation of the Insulin Receptor (InR) gene in regulating final organ size? I have addressed these questions through a variety of genetic and biochemical tools in the model system of the common fruit fly Drosophila melanogaster. In order to understand the role of hormonal signaling, I used the model of the wing imaginal disc to show that growth retardation in one part of the imaginal disc results in coordinated reduction in growth rate in the unperturbed part. Further, I show that this is mediated through systemic signaling by the insect hormone 20-hydroxyecdysone. Lastly, I demonstrate that systemic ecdysone signaling interacts with organ-autonomous insulin signaling to mediate growth coordination across the imaginal disc. To understand the role of transcriptional regulation of InR, I generated transgenic flies with increased dosage of InR. Using this transgenic fly line, I identified the minimal cis-regulatory region of InR and the effects of increased dosage of InR on aspects of fly physiology. I further show that the InR cis-regulatory region consists of multiple enhancers, which are capable of driving tissue-specific reporter gene expression. Lastly, I outline a strategy to test the role of modified transcriptional feedback to InR by the transcription factor dFoxo. Together, my results would be of broad interest to developmental biologists and contribute to our understanding of the mechanisms organ and body size regulation.
Read
