Figure 1.

The expression and function of Notch during the early stages of Nephrogenesis. The different stages of mammalian renal nephron development with normal development (on left side) compared to kidney development under deficient Notch signaling conditions (on right side). (A) The nephron progenitor state is maintained through Six2 expression which is normally repressed by Notch signaling to allow cells to begin differentiation within pre-tubular aggregates that become renal vesicles (RV). The RV have distinct segments with Notch ligands having a restricted expression in the distal compartment close to the ureteric bud UB tip. Notch deficiency within the nephron progenitors results in abnormal patterning of the RV. (B) Diagram of the developing nephron at the comma shaped stage. The renal vesicle undergoes further morphological changes from spherical body to comma shaped body. Notch deficiency results in decreased proliferation of Pax2+; Jag1+ cells. (C) Diagram of the developing nephron at the S-shaped stage, which occurs after the comma-shaped stage. The S-shaped body contains distinct proximal, medial, and distal domains. Notch components are expressed differentially in this structure and function to further define the nephron segments. Inactivation of Notch alters nephron segmentation, leads to loss of proximal and medial segments, and abnormal nephron structure.