During kidney development, the balance between nephron progenitor cell differentiation and proliferation determines the final number of nephrons and the ability of the kidney to function properly. One current model proposes that Wnt9b/β-catenin signalling induces differentiation in a subset of the progenitors, but that repression of this signal by the transcription factor Six2 is required for renewal of the remaining progenitors. On p. , Thomas Carroll and colleagues challenge this model by showing that Wnt9b/β-catenin signalling is active in both differentiating and renewing progenitor cells in the developing mouse kidney. Moreover, rather than inhibiting Wnt9b signalling in the renewing cells, Six2 acts cooperatively with Wnt9b to elicit progenitor cell expansion. By contrast, in those progenitor cells where Six2 activity is low, Wnt9b/β-catenin signalling induces differentiation. Thus, the researchers propose, the response of progenitor cells to Wnt9b/β-catenin signalling depends on the cellular environment in which the signal is received, and canonical Wnt9b signalling is able to regulate both progenitor cell expansion and differentiation in the developing kidney.
