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E. C. Bailey et al.
of this activated form of Ci appears to be mediated by Fu and Su(fu) but
the mechanism by which these proteins do so is not known. The proteolytic cleavage of Ci may have arisen in Drosophila to permit the fast
development of tissues. The fly embryo develops rapidly, with the larva
emerging about 22 h after egg laying. A short period of development
may require rapid control mechanisms, such as the posttranslational
regulation of Ci, for turning developmental signals on and off at the
appropriate time.
12.3.3 Gli Function in Vertebrates
Vertebrate homo logs of Ci comprise the Gli family of zinc finger transcription factors, Gli1, G1i2, and Gli3 (Kinzler et al. 1988; Ruppert et al.
1988; Ruppert et al. 1990). Functional studies illustrate that Gli family
members are clearly the mediators of vertebrate Hh signaling. In the
mouse, Glil is a target gene of Hh signaling; ectopic Shh expression
induces ectopic Glil (Grindley et al. 1997; Hynes et al. 1997) and in
ptc1 mutant mice, Glil transcription is derepressed (Goodrich et al.
1997; Hahn et al. 1998). Like Ci in Drosophila, ectopic expression of
Gli1 induces Hh targets such as ptc1 (Hynes et al. 1997). In mice, Shh is
essential for the proper development of the foregut and other organs
(Litingtung et al. 1998). Likewise, mice deficient for Gli2 and Gli3
show defects which suggest that these transcription factors mediate Shh
signaling in the foregut (Motoyama et al. 1998). In contrast to Drosophila, where Hh signaling posttranslationally regulates Ci protein, Gli
family members appear to be regulated by Hh family members at the
transcriptional level. Whether Gli family members undergo a proteolytic
processing event like Ci is not known. The high degree of functional
conservation in the Hh pathway demonstrated so far would argue for
conservation of these regulatory mechanisms, but to date, posttranslational modification of Gli family members has yet to be established.
E. C. Bailey et al.
of this activated form of Ci appears to be mediated by Fu and Su(fu) but
the mechanism by which these proteins do so is not known. The proteolytic cleavage of Ci may have arisen in Drosophila to permit the fast
development of tissues. The fly embryo develops rapidly, with the larva
emerging about 22 h after egg laying. A short period of development
may require rapid control mechanisms, such as the posttranslational
regulation of Ci, for turning developmental signals on and off at the
appropriate time.
12.3.3 Gli Function in Vertebrates
Vertebrate homo logs of Ci comprise the Gli family of zinc finger transcription factors, Gli1, G1i2, and Gli3 (Kinzler et al. 1988; Ruppert et al.
1988; Ruppert et al. 1990). Functional studies illustrate that Gli family
members are clearly the mediators of vertebrate Hh signaling. In the
mouse, Glil is a target gene of Hh signaling; ectopic Shh expression
induces ectopic Glil (Grindley et al. 1997; Hynes et al. 1997) and in
ptc1 mutant mice, Glil transcription is derepressed (Goodrich et al.
1997; Hahn et al. 1998). Like Ci in Drosophila, ectopic expression of
Gli1 induces Hh targets such as ptc1 (Hynes et al. 1997). In mice, Shh is
essential for the proper development of the foregut and other organs
(Litingtung et al. 1998). Likewise, mice deficient for Gli2 and Gli3
show defects which suggest that these transcription factors mediate Shh
signaling in the foregut (Motoyama et al. 1998). In contrast to Drosophila, where Hh signaling posttranslationally regulates Ci protein, Gli
family members appear to be regulated by Hh family members at the
transcriptional level. Whether Gli family members undergo a proteolytic
processing event like Ci is not known. The high degree of functional
conservation in the Hh pathway demonstrated so far would argue for
conservation of these regulatory mechanisms, but to date, posttranslational modification of Gli family members has yet to be established.