Hedgehog Signaling in Animal Development and Human Disease 213
A
B
Gene Iran cription
Fig. lA,B.A current model of Hedgehog signaling.A In the absence of Hh ligand, Ptc inhibits Hh-mediated gene transcription by blocking Smo activity. In
the cytosol, full length Ci is part of a complex that includes Cos2, Fu, and
Su(Fu) that is tethered to microtubules (MT). Without signaling, Ci is proteolytically converted into transcriptional repressor that blocks specific gene
expression in the nucleus.B Hh binding to Ptc relieves the inhibition of Smo
and activates signaling. Ci proteolysis is blocked and an activated form of Ci
enters the nucleus to induce target gene transcription. It is not known if Ci entry into the nucleus requires the disruption of the complex as depicted
related to that of the Frizzled family of Wnt receptors (AIcedo et al.
1996; van den Heuvel and Ingham 1996).
Ptc regulates Hh signaling in a second way, by binding and sequestering Hh to limit its range of action (Chen and Struhl 1996; Chen and
Struhl 1998). When Hh signals to a cell, the amounts of pte transcript
and protein are induced from low to high levels (Hidalgo and Ingham
1990; Ingham et al. 1991). Induction of Ptc by Hh has the important
consequence of restricting the range of Hh signaling. When cells are
unable to raise levels of Ptc in response to Hh, Hh protein (Taylor et al.
1993) and activity (Chen and Struhl 1996) extend beyond their normal
A
B
Gene Iran cription
Fig. lA,B.A current model of Hedgehog signaling.A In the absence of Hh ligand, Ptc inhibits Hh-mediated gene transcription by blocking Smo activity. In
the cytosol, full length Ci is part of a complex that includes Cos2, Fu, and
Su(Fu) that is tethered to microtubules (MT). Without signaling, Ci is proteolytically converted into transcriptional repressor that blocks specific gene
expression in the nucleus.B Hh binding to Ptc relieves the inhibition of Smo
and activates signaling. Ci proteolysis is blocked and an activated form of Ci
enters the nucleus to induce target gene transcription. It is not known if Ci entry into the nucleus requires the disruption of the complex as depicted
related to that of the Frizzled family of Wnt receptors (AIcedo et al.
1996; van den Heuvel and Ingham 1996).
Ptc regulates Hh signaling in a second way, by binding and sequestering Hh to limit its range of action (Chen and Struhl 1996; Chen and
Struhl 1998). When Hh signals to a cell, the amounts of pte transcript
and protein are induced from low to high levels (Hidalgo and Ingham
1990; Ingham et al. 1991). Induction of Ptc by Hh has the important
consequence of restricting the range of Hh signaling. When cells are
unable to raise levels of Ptc in response to Hh, Hh protein (Taylor et al.
1993) and activity (Chen and Struhl 1996) extend beyond their normal