Kidney development is guided by reciprocal interactions between mesenchymal and epithelial tissues. Although crosstalk between progenitors of nephrons and collecting ducts is known to play a crucial role, signalling from the interstitium has an increasingly appreciated, but still poorly understood, contribution. How the diversity of interstitial cell types is acquired in development is also unclear. Thomas Carroll and colleagues’ single cell view of the developing mouse kidney now helps fill these gaps. Initial gene expression analyses suggested an under-appreciated heterogeneity of interstitial cell types, leading the authors to perform single cell RNA-seq on E18.5 kidneys (enriched for interstitium thanks to a Foxd1 transgene). This reveals 17 distinct cellular clusters, which reflect at least 12 spatially distinct cell types as assessed with in situ hybridization. This diversity, rather than representing multiple different points on the same developmental trajectory, likely reflects the existence of multiple developmental pathways down which interstitial progenitors can go. β-Catenin is shown to have a cell autonomous role in the development of a medullary subset of the interstitium, which in turn non-autonomously affects the development of the adjacent epithelia. Finally, comparison with previously published human fetal transcriptomes suggests that interstitial heterogeneity is a conserved characteristic between mice and humans. Interested readers should look out for a complementary paper from the Carroll lab on the interstitium and pediatric kidney cancers, forthcoming in Development's Special Issue on The Origins and Mechanisms of Developmental Disorders (https://dev.biologists.org/content/147/21).
