Portrait of author

Christian Fokdal Christensen:
Genetic screen for secreted factors released from the intestinal stem cell niche in Drosophila melanogaster identifies novel roles of the Activin/TGF-β signaling pathway in adult intestinal homeostasis and adaptive growth

Date: 01-10-2022    Supervisor: Ditte S. Andersen & Julien Colombani




The intestinal tract represents a large interface between the internal and external environment where essential nutrients are digested and absorbed. Importantly, the intestinal tract is also among the most proliferative organs in the body. Intestinal stem cells (ISCs) within the intestinal epithelium divide continuously and coordination of their proliferation rate, differentiation process and cell fate decisions are dynamically tuned to ensure epithelial integrity at homeostasis and in response to a need for adaptive growth.

Using the Drosophila melanogaster midgut as a model organ, this PhD project aimed at identifying new secreted factors derived from the ISC microenvironment that control ISC activity and intestinal health and provide mechanistic insight into their function. By taking a functional in vivo cell-type specific RNAi screening approach the evolutionarily conserved activin branch of TGF-β signaling was identified as a novel candidate.

We found that the type I Activin receptor Baboon (Babo) is expressed in ISCs and their daughter cells known as enteroblasts (EBs). Babo and its’ downstream effector Smad on X (Smox) participate in regulating homeostatic cell turnover by controlling proliferation ISCs as well as maturation of EBs. Consistent with this, we found that two activins derived from the microenvironment, Activin-β and Dawdle, signals through different isoforms of the Babo receptor to promote adaptive growth in response to distinct environmental challenges. Altogether, our findings demonstrate that activins are key regulators of adult tissue homeostasis and plasticity.