McMahon Group

Project Description

The functional unit of the kidney is the nephron — hence, our focus on obtaining a thorough understanding of mammalian nephrogenesis. The current GUDMAP view of this process reflects the general view from the literature: largely two-dimensional, mouse kidney focused snapshots depict the progression of a sub-set of mesenchymal nephron progenitors through a mesenchymal to epithelial transition, followed by the complex morphogenesis and patterning process that establishes the nephron. To augment this understanding of the mammalian kidney, we can now harness recent advances in both static and live dynamic cell imaging, the access to human fetal kidney specimens and the development of pluripotent stem cell (PSC) culture-seeded nephrogenesis. With this goal, we will generate comparative 4D views of nephron development in the mouse and human, extending these studies to the imaging of selected mutants in the nephrogenic program. Given the recent advances in the directed differentiation of PSCs into nephron-like structures, a benchmark for normal nephrogenesis will have considerable value to the emerging field of regenerative kidney biology.