Fig. 1

Regulatory networks for branching morphogenesis. a The network motif shared by all the ligand–receptor pairs that give rise to Turing patterns. b Receptors (R) and ligands (L) are expressed in two different tissue layers. The core signalling networks that have been described to regulate branching morphogenesis in c lung and prostate, d salivary gland, and e kidney. c, d Fgf10 is expressed in the mesenchyme (grey) and binds to its receptor FGFRIIb in the epithelium (red). FGF10-bound receptors direct the outgrowth of the bud. FGF10 and SHH engage in a negative feedback, in that FGF10 signalling reduces Shh expression in the lung and prostate and increases it in the salivary gland, while SHH signalling increases Fgf10 in the lung and prostate and reduces it in the salivary gland. All ligand–receptor signalling also increases the expression of the receptor. e In the kidney, Gdnf is expressed in the mesenchyme (grey) and binds to its receptor RET in the epithelium (red). GDNF signalling induces bud outgrowth and stimulates expression of the receptor Ret and of the secreted ligand Wnt11. WNT11, in turn, increases Gdnf expression in the metanephric mesenchyme. Panels c–e were adapted from ref. ³