Balancing Renewal and Differentiation of Progenitor Cells in the Developing Kidney

Mammalian kidneys perform the important function of blood filtration. All the filtered wastes are concentrated into urine and excreted from the body. The kidney performs these functions through individual functional units called nephrons. While nephron number may decrease during one's lifetime (due to various kidney injuries or hypoxic events), new nephrons do not form in adults. This is most likely due to the absence of nephron precursor cells. If nephron number falls below a certain threshold, the kidneys stop functioning properly pre-disposing individuals to a myriad of medical conditions including renal failure. While dialysis is a treatment option, the survival rate of a dialysis patients is poor. Currently, kidney transplantation is the only long-term treatment possible, but sufficient numbers of transplantable kidneys are not available. Various stem cell therapies and kidney re-engineering are actively being pursued as viable treatment paths. For successful progress in those approaches, we need access to lots of progenitors. To obtain this a thorough understanding of kidney development and the various signals that play important roles in nephron endowment is imperative. Despite many decades of work invested in this field, there are still many unknowns. Regulation of renewal and differentiation of the progenitors during the process of nephron formation is the focus of my dissertation.