Nephrons, the basic filtering units of the mammalian kidney, are generated in the so-called nephrogenic zone (NZ) of the developing kidney over several days. This means that nephron progenitor cells must be replenished while new nephrons differentiate, a balance that depends on the growth factor BMP7, but not on the canonical BMP7-triggered response, SMAD-mediated transcriptional activation. Leif Oxburgh and co-workers now report that in mouse nephron progenitors, BMP7 induces Jun N-terminal kinase (JNK) signalling instead (see ). The researchers developed a novel cell culture system to study isolated NZ cells and demonstrate that these cells, like NZ cells in vivo, are unresponsive to SMAD-mediated signalling. Rather, they rapidly activate JNK signalling in response to BMP7, and BMP7 promotes their proliferation. Correspondingly, JNK signalling is disrupted in Bmp7-null kidneys in vivo. Together, these data suggest that BMP7 promotes nephron progenitor proliferation by directly activating JNK signalling and establish a new experimental system for investigating nephrogenesis.
