DK – University of Copenhagen
Identification of paracrine and systemic signals controlling adult stem cell activity and organ homeostasis

Identification of paracrine and systemic signals controlling adult stem activity and organ homeostasis

Multicellular organisms have evolved organs and tissues with highly specialized tasks. For instance, nutrient are taken up by the gut, sensed, processed, stored and released by the adipose tissues and liver, and utilized by peripheral organs. The function of each organ is modified by local clues and systemic signals derived from other organs to ensure a coordinated response accommodating the physiological needs of the organism. The field of inter-organ communication has increased exponentially in the last 10 years, largely due to the development of sophisticated genetic tools. Studies have shown that organ systems as well as the signals mediating inter-organ communication are highly conserved between vertebrates and insects. This in combination with the genetic amenability of flies have made Drosophila a top-choice model for studying inter-organ communication. The intestine represents one of the largest interfaces with the external environment and therefore plays a key role in relaying environmental inputs to other organs to produce a systemic response. As a primary digestive organ, the intestine is constantly exposed to a multitude of stresses including pathogenic microorganisms. To maintain barrier function and protect organismal health, the gut has developed a remarkable capacity for tissue self-renewal. At steady-state turnover rates, the intestine undergoes complete self-renewal every 4-5 days, a process which is highly accelerated in response to damage of the gut epithelium. This capacity for self-renewal relays on the proliferative activity of the intestinal stem cells (ISC), which is tightly coupled with cell loss to maintain intestinal homeostasis. ISC proliferation is controlled by multiple local and systemic signals released from neighboring cell populations and non-gastrointestinal organs. Due to the relative ease of conducting large-scale functional screens, the fly gut therefore represents an ideal system for 1) identifying intra- and inter-organ circuitries controlling adult organ homeostasis and 2) studying the systemic effects of altered organ homeostasis.