Abstract The chicken embryo is a widely used model for studying vertebrate limb development because of its ease of access and genetic and pharmacologic manipulation. During the formation of limbs the Growth Differentiation Factor 5 (GDF5) plays an essential role; it is expressed in the mesenchymal condensations that determine the cartilaginous anlagen, and later its expression shifts towards future joint zones and is therefore widely used as a genetic marker of joint development. Homozygous loss-of-function of GDF5 in humans is linked to acromesomelic chondrodysplasias, characterized by severe shortening of the limbs and absence of digits. Recently, a SNP in the promoter region of GDF5 reducing its transcription rate could be linked to osteoarthritis susceptibility. Heterozygous point mutations of GDF5 cause a spectrum of hand malformations like shortening of phalanges (brachydactyly) or joint fusions (proximal symphalangism or multiple synostosis syndrome). By functional analysis using the chicken as model organism, we have demonstrated that distinct interruptions of protein-protein interactions between GDF5 and its receptors or its antagonists are the cause for the distinct phenotypes: brachydactyly mainly caused by reduced receptor activation, whereas joint fusions resulting from insensitivity towards the antagonist NOGGIN.
Disclosure of Interest None Declared