200
A. Vortkamp
Comparative analysis of Ihh and BMP expression at chondrocyte
differentiation stages in the developing chick embryo (day 8) revealed
changes in the level of expression of BMP2, BMP4, BMP5, BMP6, and
BMP7 that correlate well with the borders of the Ihh expression domain.
BMP7 is expressed in the perichondrium flanking the hypertrophic and
prehypertrophic chondrocytes, but not distal to the border ofIhh expression. BMP2 and BMP4 are strongly expressed in the same region, and
weaker expression domains reach distal towards the ends of the skeletal
elements. BMP5 shows complementary expression levels with a weaker
expression level flanking the Ihh expression domain and a higher expression level outside the borders of the Ihh expression domain (Pathi et
al. 1999). BMP6 is expressed in the prehypertrophic and hypertrophic
chondrocytes (Vortkamp et al. 1996) whereas the BMPR-IA expression
is found in prehypertrophic chondrocytes only (Zou et al. 1997). In
addition, at least BMP2, BMP4, and BMPR-IA are strongly expressed
in the perichondrium of the joint region (Pathi et al. 1999; Zou et al.
1997). The correlation of BMP expression with that of Ihh suggests that
the two signaling pathways might interact with each other in regulating
cartilage development.
11.5.2 Ihh Regulates BMP Expression
It has been shown that misexpression of BMP4 (Duprez et al. 1996), as
well as misexpression of a constitutively active form of BMPR-IA (Zou
et al. 1997), in wings of developing chick embryos results in a massive
overgrowth of the wing skeletal elements. The morphological and molecular analysis of skeletal elements infected with a constitutively active
BMPR-IA revealed that activation of BMP signaling prevents chondrocyte differentiation in a manner similar to that of misexpression of Ihh
(Zou et al. 1997). Like Ihh misexpression, ecotopic BMP signaling activates PTHrP expression in the periarticular perichondrium implicating an
interaction of the Ihh and BMP pathways. The upregulation ofPTHrP in the
perichondrium is not accompanied by an upregulation of Ihh, indicating
that BMP signaling acts downstream of Ihh (Zou et al. 1997).
To test this hypothesis we analyzed the effect of Ihh misexpression
on the expression of various BMP genes in the perichondrium. In
principal there are two ways BMP expression can respond to Ihh misex-
A. Vortkamp
Comparative analysis of Ihh and BMP expression at chondrocyte
differentiation stages in the developing chick embryo (day 8) revealed
changes in the level of expression of BMP2, BMP4, BMP5, BMP6, and
BMP7 that correlate well with the borders of the Ihh expression domain.
BMP7 is expressed in the perichondrium flanking the hypertrophic and
prehypertrophic chondrocytes, but not distal to the border ofIhh expression. BMP2 and BMP4 are strongly expressed in the same region, and
weaker expression domains reach distal towards the ends of the skeletal
elements. BMP5 shows complementary expression levels with a weaker
expression level flanking the Ihh expression domain and a higher expression level outside the borders of the Ihh expression domain (Pathi et
al. 1999). BMP6 is expressed in the prehypertrophic and hypertrophic
chondrocytes (Vortkamp et al. 1996) whereas the BMPR-IA expression
is found in prehypertrophic chondrocytes only (Zou et al. 1997). In
addition, at least BMP2, BMP4, and BMPR-IA are strongly expressed
in the perichondrium of the joint region (Pathi et al. 1999; Zou et al.
1997). The correlation of BMP expression with that of Ihh suggests that
the two signaling pathways might interact with each other in regulating
cartilage development.
11.5.2 Ihh Regulates BMP Expression
It has been shown that misexpression of BMP4 (Duprez et al. 1996), as
well as misexpression of a constitutively active form of BMPR-IA (Zou
et al. 1997), in wings of developing chick embryos results in a massive
overgrowth of the wing skeletal elements. The morphological and molecular analysis of skeletal elements infected with a constitutively active
BMPR-IA revealed that activation of BMP signaling prevents chondrocyte differentiation in a manner similar to that of misexpression of Ihh
(Zou et al. 1997). Like Ihh misexpression, ecotopic BMP signaling activates PTHrP expression in the periarticular perichondrium implicating an
interaction of the Ihh and BMP pathways. The upregulation ofPTHrP in the
perichondrium is not accompanied by an upregulation of Ihh, indicating
that BMP signaling acts downstream of Ihh (Zou et al. 1997).
To test this hypothesis we analyzed the effect of Ihh misexpression
on the expression of various BMP genes in the perichondrium. In
principal there are two ways BMP expression can respond to Ihh misex-