Roles of FGF-10 on the development of diathrodial limb joints.
OBJECTIVE
Members of the fibroblast growth (FGF) family of signaling proteins are known to play important roles in limb skeletal patterning and in chondrocyte proliferation and maturation. Recent work from this laboratory showed that FGF members are expressed in limb developing joints. Thus, the present project focused on what roles these proteins may have in joint development.


METHODS
Heparin-coated beads precoated with recombinant FGF-10 or GDF-5 were implanted around incipient proximal and distal joints of digits 3 and 4 in Day 6-8 chick limb buds in organ culture. Specimens were processed for whole mount in situ hybridization using antisense riboprobes encoding chick GDF-5 and FGF-10 or for histology analysis at indicated time points.


RESULTS
Whole mount in situ hybridization revealed that FGF-10 is expressed, and its transcripts are present, during interzone formation. Gain-of-function experiment revealed that exogenous FGF-10 caused down-regulation of expression of FGF-10 as well as GDF-5. In specimens continuously treated with exogenous FGF-10, joint formation was markedly impaired and often resulted in fusion of contiguous cartilaginous phalanges.


CONCLUSIONS
The study provides evidence for the first time that FGF-10 is expressed during joint development in addition to FGF-2 and FGF-4. The precise roles of these signaling molecules will require further work. However, it is possible to speculate that these proteins, singly or in concert, may favor proliferation of mesenchymal cells during interzone formation. Our data also show that prolonged treatment with exogenous FGF-10 leads to joint impairment and fusion. Similar defects were observed previously when other joint-associated proteins were experimentally manipulated, indicating that a fine balance among distinct regulatory molecules is needed for normal joint formation.
Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, USA.
Irina
I
Lovinescu
E
E
Koyama
M
M
Pacifici
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects / Q000196:embryology; D002642:Chick Embryo; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000502:physiology*; D055428:Growth Differentiation Factor 5; D007596:Joints / Q000187:drug effects / Q000196:embryology*; D018878:Limb Buds / Q000196:embryology; D009924:Organ Culture Techniques; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D019485:Bone Morphogenetic Proteins; D051526:Fibroblast Growth Factor 10; D055428:Growth Differentiation Factor 5; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors