The Indian Hedgehog - PTHrP System in Bone Development
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riosteum can reciprocally influence the expression of Ihh in the differentiation chondrocytes.
11.5.3 BMP Antagonists in Developing Skeletal Elements
BMP signaling can be regulated by several antagonists including Noggin and Chordin (Hirsinger et al. 1997; Marcelle et al. 1997; Reshef et
al. 1998; Sasai et al. 1994; Smith and Harland, 1992; Smith et al. 1993).
Both are secreted molecules which can bind to different BMPs and
prevent them from binding to their receptors (Piccolo et al. 1997; Piccolo et al. 1996; Zimmerman et al. 1996). Recently it has been shown
that Noggin and Chordin are both expressed in the developing cartilage
elements. Noggin is initially expressed in the early cartilage condensations. As the skeletal elements develop, Noggin expression becomes
progressively restricted to the ends of the cartilage elements distal to the
proliferating chondrocytes. In addition, low levels of Noggin expression
can be found in the proliferating and differentiating chondrocytes,
whereas the hypertrophic chondrocytes no longer express Noggin (Capdevila and Johnson 1998; McMahon et al. 1998; Merino et al. 1998;
Pathi et al. 1999). At cartilage differentiation stages, Chordin is expressed in the periarticular region of the cartilage elements in a domain
overlapping with, but wider than that expressing PTHrP (Pathi et al.
1999). The similarity of the expression domains of PTHrP and Chordin
indicates that Chordin might be regulated by Ihh in a similar manner as
was shown for PTHrP. We analyzed the expression of Chordin after Ihh
misexpression in embryonic chick limbs on E8 and found that, like
PTHrP, chordin was strongly upregulated in the periarticular perichondrium. We also analyzed the expression of Noggin after Ihh misexpression and found Noggin throughout the cartilage element, most likely as
a result of the block of chondrocyte differentiation (Pathi et al. 1999).
Together these data indicate that Ihh regulates BMP signaling, not
only by regulating the expression of several BMP genes but also by
influencing the expression of antagonists of BMP signaling at least
Noggin and Chordin.
203
riosteum can reciprocally influence the expression of Ihh in the differentiation chondrocytes.
11.5.3 BMP Antagonists in Developing Skeletal Elements
BMP signaling can be regulated by several antagonists including Noggin and Chordin (Hirsinger et al. 1997; Marcelle et al. 1997; Reshef et
al. 1998; Sasai et al. 1994; Smith and Harland, 1992; Smith et al. 1993).
Both are secreted molecules which can bind to different BMPs and
prevent them from binding to their receptors (Piccolo et al. 1997; Piccolo et al. 1996; Zimmerman et al. 1996). Recently it has been shown
that Noggin and Chordin are both expressed in the developing cartilage
elements. Noggin is initially expressed in the early cartilage condensations. As the skeletal elements develop, Noggin expression becomes
progressively restricted to the ends of the cartilage elements distal to the
proliferating chondrocytes. In addition, low levels of Noggin expression
can be found in the proliferating and differentiating chondrocytes,
whereas the hypertrophic chondrocytes no longer express Noggin (Capdevila and Johnson 1998; McMahon et al. 1998; Merino et al. 1998;
Pathi et al. 1999). At cartilage differentiation stages, Chordin is expressed in the periarticular region of the cartilage elements in a domain
overlapping with, but wider than that expressing PTHrP (Pathi et al.
1999). The similarity of the expression domains of PTHrP and Chordin
indicates that Chordin might be regulated by Ihh in a similar manner as
was shown for PTHrP. We analyzed the expression of Chordin after Ihh
misexpression in embryonic chick limbs on E8 and found that, like
PTHrP, chordin was strongly upregulated in the periarticular perichondrium. We also analyzed the expression of Noggin after Ihh misexpression and found Noggin throughout the cartilage element, most likely as
a result of the block of chondrocyte differentiation (Pathi et al. 1999).
Together these data indicate that Ihh regulates BMP signaling, not
only by regulating the expression of several BMP genes but also by
influencing the expression of antagonists of BMP signaling at least
Noggin and Chordin.