Characterization of the Role of Shroom3 in Nephron Formation
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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.
