192
A. Vortkamp
lage by bone. The chondrocytes in the cartilage elements are surrounded
by a thin layer of flattened cells, the perichondrium. In parallel with the
differentiation of hypertrophic chondrocytes, the perichondrium flanking the differentiating and hypertrophic chondrocytes differentiates into
an osteoblast-containing periosteum, which secretes a layer of primary
bone, the bone collar. Signals from the perichondrium/periosteum are
thought to interact with signals from the cartilage itself in correlating
hypertrophic differentiation with the differentiation of the perichondrium into a periosteum. To understand the process of endochondral
ossification it is necessary to identify the specific signals regulating the
different steps in this process and to analyze their interactions.
11.2 Indian Hedgehog Signaling During Chondrocyte
Differentiation
11.2.1 Expression of Ihh
Recently, we and others (Bitgood and McMahon 1995; Vortkamp et al.
1996) have identified a secreted signaling factor, Indian Hedgehog
(Ihh), which is expressed in the developing cartilage elements. Comparative expression analysis with chondrocyte markers (Col-II marks all
chondrocytes, whereas Col-X specifically marks hypertrophic chondrocytes) reveals that Ihh expression starts during the early steps of bone
development in mice and chick. At the early stages Ihh is expressed in
the center of the condensing cartilage elements shortly after the chondrocytes are formed. With the onset of hypertrophic differentiation, Ihh
expression becomes restricted to the differentiating chondrocytes. At
this stage, proliferating and terminally differentiated, hypertrophic
chondrocytes do not express Ihh. Therefore, Ihh can be regarded as
being specifically expressed in chondrocytes that are actively undergoing hypertrophic differentiation.
A. Vortkamp
lage by bone. The chondrocytes in the cartilage elements are surrounded
by a thin layer of flattened cells, the perichondrium. In parallel with the
differentiation of hypertrophic chondrocytes, the perichondrium flanking the differentiating and hypertrophic chondrocytes differentiates into
an osteoblast-containing periosteum, which secretes a layer of primary
bone, the bone collar. Signals from the perichondrium/periosteum are
thought to interact with signals from the cartilage itself in correlating
hypertrophic differentiation with the differentiation of the perichondrium into a periosteum. To understand the process of endochondral
ossification it is necessary to identify the specific signals regulating the
different steps in this process and to analyze their interactions.
11.2 Indian Hedgehog Signaling During Chondrocyte
Differentiation
11.2.1 Expression of Ihh
Recently, we and others (Bitgood and McMahon 1995; Vortkamp et al.
1996) have identified a secreted signaling factor, Indian Hedgehog
(Ihh), which is expressed in the developing cartilage elements. Comparative expression analysis with chondrocyte markers (Col-II marks all
chondrocytes, whereas Col-X specifically marks hypertrophic chondrocytes) reveals that Ihh expression starts during the early steps of bone
development in mice and chick. At the early stages Ihh is expressed in
the center of the condensing cartilage elements shortly after the chondrocytes are formed. With the onset of hypertrophic differentiation, Ihh
expression becomes restricted to the differentiating chondrocytes. At
this stage, proliferating and terminally differentiated, hypertrophic
chondrocytes do not express Ihh. Therefore, Ihh can be regarded as
being specifically expressed in chondrocytes that are actively undergoing hypertrophic differentiation.