Current Research
Growth is fundamental to development, yet remarkably little is known about the mechanisms that control organ size. How do cells know when to stop dividing after an organ has reached its proper size and how do injured organs regenerate missing or damaged parts? The answers to these questions are currently not known, but a common theme appears to be that cells signal to each other to regulate cell proliferation and organ growth. What are these signals and how do they regulate organ growth? We are using the fruit fly Drosophila as a model system to address these questions and to discover novel signaling pathways that regulate growth and regeneration. The combination of the powerful genetic tools and the capability of its developing tissues to regenerate make Drosophila a superb system in which to study growth control and regeneration.
To discover novel growth control genes we carried out several genome-wide genetic screens through which we discovered a novel growth control pathway that we named the “Hippo pathway”. We and others identified several components of the Hippo pathway and it turns out that the Hippo pathway is a novel signal transduction pathway from the membrane receptor Fat over the Hippo kinase into the nucleus where the pathway regulates gene expression. Importantly, animals carrying mutations in Hippo pathway components develop severely overgrown structures and have tumorous outgrowths. The Hippo pathway is thus essential to regulate normal organ size. Strikingly, the Hippo pathway is highly conserved in vertebrates where it also regulates growth and is involved in cancer. However, how the Hippo pathway is regulated and what role it plays during normal growth and regeneration is not known. We are currently investigating novel extracellular signals that regulate the Hippo pathway and how Hippo signaling and other pathways are involved in the control of organ growth and regeneration.
Diagram of the canonical Hippo pathway
Wild-type fly and fly with hippo mutant
tissue displaying an overgrowth phenotype