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. 2013 Sep;3(9):130088. doi: 10.1098/rsob.130088

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© 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.

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Figure 4. — Signalling networks in branching morphogenesis. The core signalling networks that have been described to regulate branching morphogenesis in (a) lung and prostate, (b) salivary gland, (c) pancreas and (d) kidney are shown. In the lung, prostate, salivary gland and pancreas FGF10 (F) signalling directs outgrowth of the epithelium. Fgf10 is expressed in the mesenchyme (grey) and binds to its receptor (R) in the epithelium (red). FGF10-bound receptor not only directs outgrowth, but also regulates expression of Shh (S) ((a) upregulation in the lung and prostate, (b) downregulation in the salivary gland, (c) no reported regulation in the pancreas). SHH binds its receptor PTCH1 (P) and the SHH-receptor complex, in turn, regulates Fgf10 expression ((a,c) downregulation in the lung, prostate and pancreas, (b) upregulation in the salivary gland). All ligand–receptor signalling also upregulates the expression of the receptor. (d) In the case of the ureteric bud, GDNF (G) induces bud outgrowth and GDNF-receptor binding stimulates expression of the receptor Ret and of Wnt11 (W) in the epithelium. WNT11, in turn, causes upregulation of Gdnf expression in the mesenchyme.