Cell lineages in the embryonic kidney: their inductive interactions and signalling molecules

The first signalling genes acting in the inductive interactions in the kidn ey have now been identified. Differentiation of the permanent kidney or the metanephros is critically dependent on inductive signalling between the ne phrogenic mesenchyme and ureteric bud epithelium. Further inductive interac tions occur between developing nephrons, interstitial stroma, endothelial c ells and neurones. Glial-cell-line-derived neurotrophic factor is a signal for the ureteric bud initiation and branching, and Wnt4 is an autocrine epi thelializing signal at the pretubular stage of nephron formation. The signa ls for renal angiogenesis and innervation are less well defined, but seem t o include vascular endothelial growth factor and neurotrophins, at least. T he ureteric-bud-derived signal for induction of the nephrogenic mesenchyme (to bring the cells to the condensate stage) is not yet known, but fibrobla st growth factor 2 is a good candidate. None of the signalling genes identi fied from the embryonic kidney is specific to the organ, which raises some general questions. How do the organs develop from similar rudiments to vari ous patterns with different cell types and functions? Does the information for organ-specific differentiation pathways retain in the epithelial or mes enchymal compartment? The present, rather fragmentary molecular data would favour the view that similar molecules acting in different combinations and developmental sequences, rather than few organ-specific master genes, coul d be responsible for the divergence of patterning.