Model of how SHH and HH signaling direct various cellular programs in early ureter development.

<p>SHH is secreted from the ureteric epithelium and activates in the mesenchyme a SMO-dependent signaling pathway that induces expression of <i>Foxf1</i> in the inner mesenchymal domain. FOXF1, in turn activates and/or maintains expression of <i>Bmp4</i>. BMP4 regulates mesenchymal and epithelial proliferation, and epithelial differentiation. SMC differentiation depends both on <i>Bmp4</i> and <i>Foxf1</i>. Note that <i>Foxf1</i> 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 <i>Foxf1</i> and <i>Bmp4</i>.</p>