Endocrine Abstracts

During development, the control of growth (mass increase) and cell division ensures that animals grow to reproducible sizes and contain cells that are consistent in size and number. We are interested in understanding more about how growth is regulated during development to achieve this. By studying the development of Drosophila imaginal discs (simple epithelial structures that give rise to the epidermal structures of the adult fly), we have found that signalling via a pathway analogous to the mammalian insulin/PI 3-kinasepathway regulates growth and size. For example, increasing signalling via Drosophila PI 3-kinase (Dp110) increases growth, cell size and final organ size, whereas inhibiting signalling via Dp110 reduces growth, cell size and final organ size.
To exploit the genetic possibilities offered by Drosophila, we performed a genetic interaction screen to identify other genes involved in growth regulation. Randomly mutagenised flies were screened for mutations that dominantly enhance or suppress a small wing phenotype generated by inhibiting PI 3-kinase activity during wing development. One group of enhancer mutations isolated in the screen showed a complex genetic interaction pattern and represents at least 4 different genes. We have characterised one of these genes in more detail and named it pixie as weak hypomorphic mutations in pixie give rise to small flies. Certain aspects of the pixie phenotype resemble the phenotypes generated by mutation of genes encoding ribosomal proteins and other proteins involved in translation. pixie encodes a soluble ATP-binding cassette (ABC) protein that has not previously been implicated in translation. However, biochemical assays suggest that pixie also influences growth via effects on translation. The way in which mutations in pixie and other genes that affect translation impact upon growth during development will be discussed.