Characterization of the Role of Shroom3 in Nephron Formation

Abstract

Proper development of the nephron, the functional unit of the kidney, is essential for kidney function. The nephron develops from a pool of cap mesenchymal cells, as defined by a cluster of cells adjacent to the ureteric bud tips of branching ureteric epithelium, giving rise to two subset populations: the self renewing cells and the nephron progenitors. These nephron progenitors undergo mesenchymal-epithelial transition (MET) to develop into polarized renal vesicles (RV), and eventually fuse with the epithelial tubule to develop into a mature nephron. Although these processes are essential for the formation of functional kidneys, little is known about the molecular mechanisms that regulate them. In this study, we characterize several steps during cap mesenchyme and renal vesicle formation using our Shroom3 knockout mouse kidney as our model. Previous researchers have associated Shroom3 with chronic kidney disease. Detecting and analyzing the genetic components of CKD is needed to improve our understanding of its pathogenesis. Shroom3 encodes an actin-binding protein that regulates cell shape changes through induction of apical constriction. However, there is a lack of evidence about Shroom3’s expression pattern and functional role upstream of developed nephrons. Here, I defined the spatial and temporal expression of Shroom3 within the cap mesenchyme region. I investigated the nephron progenitors between Shroom3 wildtypes and mutants. Lastly, I analyzed the renal vesicle polarity in mutants, by analyzing apical membrane markers on RVs to characterize any abnormalities in their orientation and establishment of polarity.