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Nephron patterning

The kidney nephron is partitioned during development into tubule segments with distinct functions. Nephron patterning studies reveal cell signaling and transcriptional events that define kidney cell types.

The paired domain transcription factor pax2a establishes the boundary between podocytes and the neck segment of the nephron. Mutation in pax2a (no isthmus, noi) results in expanded expression of the podocyte markers wt1a and vegf into the neck and proximal tubule and repression of proximal convoluted tubule marker expression (NaK ATPase, 3G8). Thus pax2a defines the podocyte/neck/proximal tubule boundaries, possibly by repressing podocyte-specific genes in the neck and proximal tubule segments.

Our studies revealed that Notch signaling and lateral inhibition generates a mosaic pattern of tubule cell types in the pronephric nephron. We showed that Notch signaling can rescue cilia-driven fluid flow and the cystic kidney mutant phenotype by producing more pronephric multiciliated cells. Thus nephron function can be altered by changing the relative proportions of nephron cell types. Similar cell signaling events have been found to pattern the mammalian lung and kidney.