IMP Research Report 2002

Figure 2: In ovo gain-of-function experiment with chick using retroviral injections to investigate the potential role of different factors in skeletogenesis.
(A) Injections of retroviral particles are performed at day 3.5 of chick embryonic development into the posterior half anlage of the future wing (w).
(B) Schematic drawing of the injected limb bud (injected region is colored blue). (C) Visualization of the infection two days after the injection, shown by
the blue staining. (D) Visualization of morphological changes six days after the injection, showing the effects of the gain-of-function experiment on the
skeletal elements of the right (R) wing while the left (L) wing is unaffected (cartilage elements are stained blue).
a role in mouse skeletogenesis at all using a conditional
gene targeting approach. Recent reports have
implicated Wnt-signaling in the control of bone
development and maintenance (Hartmann and Tabin,
2000; Kato et al., 2002). In particular, we are interested
in analyzing potential roles of Wnt4 and Wnt14 in bone
homeostasis using both, chick and mouse.
Synovial joint development
Our recent analysis of the role of Wnt14 in chick
skeletogenesis has identified Wnt14 as a major player
in the induction process of synovial joint development
(Hartmann and Tabin, 2001). However, in various cell
culture systems, Wnt14 alone is unable to induce the
Figure 3: Section through the joint of a chicken knee. Cartilage is
stained in red, soft tissue is stained greenish, perichondrium (P)
and ligaments (L) in the joint are stained in dark blue.
same responses as in ovo. Thus, we are trying now to
establish an in vitro co-culture system in order to identify
co-factors required for the induction of markers
characteristic of the early joint interzone.
We are also investigating whether Wnt14 is necessary
for joint development in the mouse model system. In
addition, since Wnt14 continues to be expressed in
synoviocytes of the mature joint, we would like to
determine whether Wnt14 plays a role in maintaining
joint integrity. This late expression of Wnt14 is very
interesting in light of joint diseases associated with
alterations of the synovium, such as rheumatoid- or
Our long-term goals are to identify regulators as well
as target genes of Wnt14. Using a transgenic approach
in combination with searching for evolutionary highly
conserved genomic regions within the Wnt14 locus we
are attempting to identify regulatory elements
responsible for the expression in the early joint
interzone. The identification of such a joint specific
element will provide a useful tool to address the question
which factors are necessary for initiation and regulation
of Wnt14 in the joint forming region and will inevitably
allow us to understand how the skeleton is patterned.
osteoarthritis. We are currently addressing potential late
function(s) of Wnt14 in the joint using gain- and lossof-function
experiments.
Contact: hartmann@imp.univie.ac.at
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