A complex signaling pathway involving members of the Hedgehog, Bone 
morphogenetic protein (Bmp) and Gli families regulates early patterning events 
in fetal skeletogenesis (Hui and Joyner, 1993. A mouse model of Greig 
cephalopolysyndactyly syndrome: the extra-toes mutation contains an intragenic 
deletion of the Gli3 gene. Nat. Genet. 3, 241-246; Bitgood and McMahon, 1995. 
Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell 
interaction in the mouse embryo. Dev. Biol. 172, 126-138; Lanske et al., 1996. 
PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone 
growth. Science 273, 663-666; Vortkamp et al., 1996. Regulation of rate of 
cartilage differentiation by Indian hedgehog and PTH-related protein. Science 
273, 613-622). Hedgehog genes encode secreted proteins that mediate patterning 
and growth through the induction of secondary signals (reviewed in Hammerschmidt 
et al., 1997. The world according to hedgehog. Trends Genet. 13, 14-21). Two 
potential targets of Ihh are bmp6 and gli (Johnson et al., 1995. Patched 
overexpression alters wing disc size and pattern: transcriptional and 
post-transcriptional effects on hedgehog targets. Development 121, 4161-4170; 
Dominguez et al., 1996. Sending and receiving the hedgehog signal: control by 
the Drosophila Gli protein Cubitus interruptus. Science 272, 1621-1625; Marigo 
et al., 1996. Sonic hedgehog differentially regulates expression of GLI and GLI3 
during limb development. Dev. Biol. 180, 273-283). We investigated the molecular 
similarities and differences between fetal and postnatal skeletal development by 
analyzing the coincident and complimentary expression domains of indian hedgehog 
(ihh), bmp6 and gli in adjacent sections throughout the process of 
skeletogenesis. In almost all of the skeletal tissues examined, the expression 
domains of ihh and bmp6 were adjacent to one another and this region was 
surrounded by gli-expressing cells. These observations are in keeping with the 
proposed function of gli as a negative regulator of Ihh signaling and the 
induction of Bmps by Hedgehog proteins (Roberts et al., 1995. Sonic hedgehog is 
an endodermal signal inducing Bmp-4 and Hox genes during induction and 
regionalization of the chick hindgut. Development 121, 3163-3174; Kawakami et 
al., 1996. BMP signaling during bone pattern determination in the developing 
limb. Development 122, 3557-3566). By puberty, ihh, bmp6 and gli transcripts 
were no longer detected in the growth plate, despite the fact that physeal 
chondrocytes continued to hypertrophy and differentiate. Although bmp6 was 
expressed, ihh transcripts were not found in primordia of intramembranous bones, 
nor in cells lining the future articular surfaces. Collectively our findings 
suggest that ihh participates in, but is not required for chondrocyte 
hypertrophy.