Cell Fate Decision
Dividing Drosophila intestinal stem cell displaying asymmetric distribution of an essential cell fate determinant
During each stem cell division, precise mechanisms insure that newly formed cells differentiate into the correct cell type that is required to maintain long-term homeostasis of their resident tissue. We have recently identified a novel mechanism controlling this process in the Drosophila intestine. It involves a cell surface receptor and its ligand, which have not yet been recognized as stem cell regulators. We are now investigating the detailed molecular mechanisms that are involved and the influence of aging on this signaling pathway.
As part of our previous studies of the Drosophila digestive tract, we identified a signaling protein specifically secreted by endocrine cells in the intestinal epithelium. Interestingly, its receptor is exclusively expressed by the stem cell population. These findings and follow-up experiments demonstrated that stem cells constantly survey their microenvironment for the presence of functional differentiated cells and, as a result, adapt the expression of key specification factors to promote differentiation of the exact cell type required for tissue maintenance.
Although we have extensively characterized the role of this pathway in the cell-fate decision process, the molecular mechanisms underlying this regulation are largely unknown and are currently under investigation in our lab. In addition, we observed dramatic age-related defects in this pathway and are now exploring its interaction with stress signaling, the intestinal immune response and the aging process
Dividing Drosophila intestinal stem cell displaying symmetric distribution of cell fate determinants