Model of how SHH and HH signaling direct various cellular programs in early ureter development.
SHH is secreted from the ureteric epithelium and activates in the mesenchyme a SMO-dependent signaling pathway that induces expression of Foxf1 in the inner mesenchymal domain. FOXF1, in turn activates and/or maintains expression of Bmp4. BMP4 regulates mesenchymal and epithelial proliferation, and epithelial differentiation. SMC differentiation depends both on Bmp4 and Foxf1. Note that Foxf1 requires an additional (epithelial) signaling input to upregulate and confine it to the inner mesenchymal domain. SMO-mediated HH signaling also directs cell survival in the outer mesenchymal domain but this activity is independent of Foxf1 and Bmp4.