View Program - 63rd Annual Drosophila Research Conference

An animal’s long-term survival requires that its organs adapt to unpredictable environmental changes. Yet how do mature organs sense external change and deploy an appropriate, reversible response? We seek the cellular and molecular basis of adult organ plasticity—i.e., the remarkable facility with which organs adaptively switch between states of renewal, remodeling, and repair. Our focus is the adult Drosophila gut, whose deep playbook of adaptive responses is executed by a multi-fated collective of stem and terminal daughter cells.
As the cell is the fundamental unit of an organ, we posit that the cell’s lifecycle—from birth to differentiation, maturity, and finally death—is the fundamental unit of an organ state. Using new techniques we devised to image functioning guts in live animals, we are resolving these surprisingly diverse lifecycles in real time. We have demonstrated the basis of conservative lifecycle kinetics that maintain the status quo, such as when the gut sustains steady-state turnover by ‘closing the loop’ between apoptosis and death through the intimate relay of a transient, spatially delimited EGF. When ingested toxins raze large swaths of differentiated cells, the damaged cells unleash cytokines that restore the status quo by concerted acceleration of stem cell divisions and daughter cell differentiation. We also have discovered non-conservative lifecycles that adapt the status quo to dietary change. For instance, when food is withdrawn, the gut quickly shrinks as mature cells abort their lifecycles and forego apoptosis to eject live from the tissue. Altogether, our findings illustrate how organ plasticity flows from extrinsically triggered tuning of single-cell lifecycles.

Origins of adult organ plasticity: How cell lifecycles define tissue states