Nephron progenitors in the metanephric mesenchyme

Abstract

The kidney is formed by a reciprocally inductive interaction between two precursor tissues, the metanephric mesenchyme and the ureteric bud. This interaction can be divided into three processes: attraction of the ureteric bud toward the mesenchyme, maintenance of the mesenchyme in an undifferentiated state versus transition to an epithelial state, and further differentiation into multiple epithelial lineages, such as glomeruli and renal tubules. In this review we describe our recent findings related to each process. A mesenchymal nuclear zinc finger protein, Sall1, controls ureteric bud attraction by regulating a novel kinesin, Kif26b. The Sall1 gene is highly expressed in multipotent nephron progenitors in the mesenchyme, and these cells can partially reconstitute a three-dimensional structure in organ cultures following Wnt4 stimulation. While Notch2 is required for further differentiation of proximal nephron structures, ectopic Notch2 activation in the embryonic kidney depletes nephron progenitors, suggesting that Notch2 stabilizes--rather than dictates--nephron fate by shutting down the maintenance of undifferentiated progenitor cells.

Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers

“…To confirm that this SIX2 expression was consistent with differentiation toward CM, we evaluated the expression of SALL1 and WT1, two other important markers of CM. 34,45 Nearly all SIX2 + cells coexpressed SALL1 as seen by immunocytochemistry, and a subset of SIX2 + cells also coexpressed WT1 ( Figure 5E). During embryonic kidney development, Wnt signals from the ureteric bud induce the CM to condense into a pretubular aggregate, which subsequently develops into a renal vesicle, comma-shaped body, S-shaped body, and ultimately a nephron.…”

Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV

“…Thus, KSHV appeared to downregulate Thy1.1 expression to inhibit its tumor-suppressive effect, while at the same time converting the mesenchymal precursor cells into a mixed phenotype of vascular and lymphatic endothelial cells. This reprogramming process is not surprising, because MM cells are multipotent and can be differentiated into diverse cell types, including endothelial cells (25,26). Nevertheless, whether mesenchymal precursor cells are the KSHV targets in vivo requires further investigation.…”

Maintenance of Mouse Nephron Progenitor Cells in Aggregates with Gamma-Secretase Inhibitor

“…MM contains multi-potent self-renewing nephron progenitor cells (NPC), which condenses around the UB tips to form the so called cap mesenchyme [10–12]. The NPC express unique combinations of transcription factors, such as Hox11 paralogs, Osr1, Pax2, Eya1, WT1, Sall1, and Six2, where Six2 and Sall1 were shown to be essential for their progenitor status [10–14].…”

“…The NPC express unique combinations of transcription factors, such as Hox11 paralogs, Osr1, Pax2, Eya1, WT1, Sall1, and Six2, where Six2 and Sall1 were shown to be essential for their progenitor status [10–14]. Upon induction from UB, NPC undergoes mesenchymal-to-epithelial transformation (MET) while migrating from UB tips to sequentially form pre-tubular renal aggregates, renal vesicles, comma- and S-shaped bodies, which further elongate to form the different segments of the nephron.…”

“…The balance between self-renewal and differentiation of NPC is important in determining the final nephron number, which can have significant health consequences [10–12]. However, our understanding on the mechanism that maintains the proliferation and the progenitor status of NPC remains limited.…”