In Drosophila, Dachsous and Fat act as ligand and receptor, respectively, for a signalling pathway that regulates planar cell polarity (PCP) and transcription via the Hippo pathway. Mammals encode multiple Fat and Dachsous proteins but do they have an equivalent Fat signalling pathway? On p. 947, Yaopan Mao and colleagues report that murine Dchs1 and Fat4 function as a ligand-receptor pair during development. The researchers show that Dchs1 and Fat4 single mutants and Dchs1 Fat4 double mutants exhibit similar phenotypes. These phenotypes include the formation of kidney cysts and cochlear defects, suggesting that Dchs1-Fat4 signalling influences PCP in mice. However, the researchers also identify non-PCP-related requirements for Dchs1-Fat4 signalling in the development of other organs. In particular, they show that Dchs1 and Fat4 are needed for growth, branching and cell survival during early kidney development. Together, these results identify Dchs1 and Fat4 as a ligand-receptor pair for mammalian Fat signalling and identify new requirements for Fat signalling in multiple organs.