99 Oral - Stem Cells, Regeneration, and Tissue Repair
Friday April 08, 11:15 AM - 11:30 AM

Authors:
Shyama Nandakumar ^1,2; NIcolas Buchon ^1,2

Affiliations:
1) Cornell Institute of Host-Microbe Interactions and Disease, Cornell University; 2) Department of Entomology, Cornell University

Keywords:
d. intestinal stem cells; k. host/pathogen interactions

Enterocytes are a well conserved cell type and make up the majority of the digestive system across metazoans. In Drosophila, enterocytes comprise nearly 90% of the adult gut epithelium, and play important roles in digestion such as secretion of digestive enzymes and absorption of nutrients, maintaining gut epithelial barriers and regulating tissue turnover. Enterocytes are also the first line of defense against oral pathogens. However, despite their critical functions, enterocytes are not as well studied as the other cells in the midgut epithelium. Enterocytes are also subject to frequent cell turnover in the midgut epithelium, a process that is acutely accelerated upon infection. What determines the decision of an enterocyte to remain in the epithelium or to delaminate? To understand this, we have developed a number of genetic tools as well as microscopy and flow cytometry based assays to study epithelial dynamics and cell turnover in the midgut over a comprehensive time course following oral infection with multiple pathogens such as Erwinia carotovora 15 (Ecc15) and Pseudomonas entomophilia (Pe). We have identified key differences between the anterior and posterior midgut in the kinetics and amplitude of cell loss and enterocyte turnover upon infection in both male and female adult flies. We observe differences in enterocyte loss in response to infection with Ecc15 and Pe. At the tissue level, we have identified mechanical changes that the midgut epithelium undergoes in response to oral pathogens such as muscle constrictions, gut contraction and region-specific changes in length. Additionally, at the cellular level, we have identified acute and dynamic changes in enterocyte cell shape, size and the nature of cell-cell junctions. We are currently investigating the genetic factors responsible for these changes, and how they impact gut physiology and infection response in the adult fly. We are also employing live imaging strategies to monitor enterocyte dynamics in vivo under various conditions. Our work will provide several key insights into the biology of enterocytes under physiological as well as pathological conditions.