The Hh signaling pathway. (a) Ptch1 is located at the base of
the primary cilium, where it inhibits Smo. Gli transcription factors are found
in the repressor form (GliR) in the cilium. Sufu can therefore
complex with Gli proteins and inhibit their nuclear localization and
transcriptional activity. (b) Upon Hh ligand binding, Ptch1
releases its repression, and Smo stimulates the accumulation of Gli factors in
the active form (GliA), which can promote the transcription of Hh
pathway target genes. Abbreviations: Boc, brother of Cdo/biregional Cdon-binding
protein; Cdo, Cell adhesion molecule–related/downregulated by oncogenes;
Evc2, Ellis van Creveld syndrome protein 2; Gas1, Growth arrest specific 1; Gli,
Glioma-associated oncogene; Hh, Hedgehog; Hip, Hedgehog-interacting protein;
Kif7, Kinesin family member 7; IFT, intraflagellar transport; Ptch1, Patched 1;
Smo, Smoothened; Sufu, Suppressor of Fused.