Formation of the adult kidney requires interactions between three adjacent cell populations of the embryonic kidney: the epithelial ureteric bud (UB), the cap mesenchyme (CM), which gives rise to nephron progenitors, and the stromal mesenchyme (stroma). How these different cell types communicate to achieve successful kidney morphogenesis is not yet fully understood. In this issue, two studies assess the contribution of Fat4 and Dchs1/2, members of the cadherin family that regulate both Hippo and planar cell polarity signalling, to the cell-cell communication required for kidney development.
On p. , Kenneth Irvine and colleagues found that, as previously described for Fat4 mutant mice, the ablation of Dchs1 leads to an expansion of the nephron progenitor pool, indicating that Fat4 and Dchs1 function as signalling partners. Interestingly, and contrary to previous studies, the authors did not observe activation of Yap in association with the CM expansion caused by Fat4 or Dchs1 depletion. Using conditional deletion of Dchs1 in different kidney populations, the authors show that Dchs1 is specifically required in CM cells, where it localizes to the cell surface that contact the stroma, to regulate their differentiation, the development of the stroma and, indirectly, that of the UB. This study sheds light on the cellular and molecular mechanisms of the cell-cell communication that orchestrates kidney morphogenesis.
In the second study (p. ), Helen McNeill and co-workers show that in the stroma, Fat4 (but not Fat1 or Fat3) interacts with Dchs1 and 2 (which act partially redundantly) to regulate CM differentiation. Interestingly, they further show that Fat4 regulates the nephron progenitor pool size independently of YAP and the core PCP Vangl2, but through Six2, a known regulator of CM size. Additionally, the authors find that Fat4 loss leads to defective cellular organization of the CM and UB-derived tubules and to the alteration of Notch and FGF pathways, providing further insight into the molecular mechanisms governing the intercellular communications that mediate kidney morphogenesis.
