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E. C. Bailey et al.
range. Thus, Ptc induction dampens the effects of the signal after it has
been received. By positively regulating its own receptor, Hh induces
high amounts of Ptc, leading to greater Ptc-Hh association and local
sequestration of the Hh signal. pte induction is a common aspect of Hh
signaling during development as it is seen in most Hh target tissues in
animals ranging from flies to mice (Concordet et al. 1996; Goodrich et
al. 1996; Marigo and Tabin 1996).
12.2.2 Vertebrate Homologs of pte
Considering the central role Ptc plays in receiving and regulating the Hh
signal, it is not surprising that vertebrates have evolved multiple pte
homologs. Currently, two murine pte genes have been identified, ptc1
(Goodrich et al. 1996) and pte2 (Takabatake et al. 1997; Carpenter et al.
1998; Motoyama et al. 1998). While both proteins have a similar proposed topology and share 54% identity overall, the proposed intracellular loop and C-terminus of Ptc2 are much shorter (Motoyama et al.
1998). When overexpressed in cultured cells, both proteins bind murine
Hh family members and associate with Smo (Marigo et al. 1996; Stone
et al. 1996; Carpenter et al. 1998). Apparently, either protein could
regulate the signaling of murine Hh family members as both Ptc 1 and
Ptc2 bind Sonic Hedgehog (Shh), Indian Hedgehog (Ihh), and Desert
Hedgehog (Dhh) with nM affinity (Carpenter et al. 1998).
The two pte homo logs are expressed in a wide range of tissues during
mouse development. ptcl is expressed at high levels adjacent to tissues
that express Hh family members, suggesting that ptc1 regulates the
signaling of all three Hh members in vivo (Bitgood et al. 1996; Goodrich et al. 1996; Vortkamp et al. 1996). As in Drosophila, the induction
of ptc1 suggests that cells have received Hh signals and have raised Ptc I
levels to sequester and restrict the amount of signaling. Genetic studies
show that ptc1 is critical in regulating Shh signaling (Goodrich et al.
1996; Hahn et al. 1998), and other evidence suggests that Ihh and Dhh
may likewise mediate their effects through Ptel in vivo (Bitgood et al.
1996; Goodrich et al. 1996; Vortkamp et al. 1996). The role of ptc2 in
mouse development is less clear. In general, pte2 is expressed in a
pattern similar to ptc1 but at much lower levels (Carpenter et al. 1998;
E. C. Bailey et al.
range. Thus, Ptc induction dampens the effects of the signal after it has
been received. By positively regulating its own receptor, Hh induces
high amounts of Ptc, leading to greater Ptc-Hh association and local
sequestration of the Hh signal. pte induction is a common aspect of Hh
signaling during development as it is seen in most Hh target tissues in
animals ranging from flies to mice (Concordet et al. 1996; Goodrich et
al. 1996; Marigo and Tabin 1996).
12.2.2 Vertebrate Homologs of pte
Considering the central role Ptc plays in receiving and regulating the Hh
signal, it is not surprising that vertebrates have evolved multiple pte
homologs. Currently, two murine pte genes have been identified, ptc1
(Goodrich et al. 1996) and pte2 (Takabatake et al. 1997; Carpenter et al.
1998; Motoyama et al. 1998). While both proteins have a similar proposed topology and share 54% identity overall, the proposed intracellular loop and C-terminus of Ptc2 are much shorter (Motoyama et al.
1998). When overexpressed in cultured cells, both proteins bind murine
Hh family members and associate with Smo (Marigo et al. 1996; Stone
et al. 1996; Carpenter et al. 1998). Apparently, either protein could
regulate the signaling of murine Hh family members as both Ptc 1 and
Ptc2 bind Sonic Hedgehog (Shh), Indian Hedgehog (Ihh), and Desert
Hedgehog (Dhh) with nM affinity (Carpenter et al. 1998).
The two pte homo logs are expressed in a wide range of tissues during
mouse development. ptcl is expressed at high levels adjacent to tissues
that express Hh family members, suggesting that ptc1 regulates the
signaling of all three Hh members in vivo (Bitgood et al. 1996; Goodrich et al. 1996; Vortkamp et al. 1996). As in Drosophila, the induction
of ptc1 suggests that cells have received Hh signals and have raised Ptc I
levels to sequester and restrict the amount of signaling. Genetic studies
show that ptc1 is critical in regulating Shh signaling (Goodrich et al.
1996; Hahn et al. 1998), and other evidence suggests that Ihh and Dhh
may likewise mediate their effects through Ptel in vivo (Bitgood et al.
1996; Goodrich et al. 1996; Vortkamp et al. 1996). The role of ptc2 in
mouse development is less clear. In general, pte2 is expressed in a
pattern similar to ptc1 but at much lower levels (Carpenter et al. 1998;