Collecting duct differentiation
The two main cell types of the collecting duct reside intermingled along the entire collecting duct system with a gradual increase in ratio of principal to intercalated cell types toward the medulla. These cell types arise from a common progenitor, but precise cell lineage relationships and molecular mechanisms patterning the collecting duct cell fates are mostly unknown. The intercalated and principal cells are responsible for water and pH homeostasis and the ratio of these cell types may adapt to physiologic stress, but whether this involves a simple expansion of a cell type, trans-differentiation, or requires reserve multi-potent precursors to undergo differentiation is unclear. We are currently examining the roles of Notch and Foxi1 in the process by which precursors (UB) of the collecting duct cell types differentiate into principal and intercalated cell types. We have performed gene expression profiling experiments using developing kidneys deficient in principal cell numbers caused by loss of Notch signaling and with a concomitant increase in intercalated cell numbers to identify potential regulators of principal and intercalated cell differentiation. We are currently characterizing the expression patterns and functions of these previously uncharacterized genes during kidney collecting duct differentiation, using genetically modified mice and using novel cell culture systems.