06-P035 Additional PEA3 binding sites in the long range limb regulator disrupt posterior restriction of SHH causing polydactyly

Idiopathic Congenital Talipes Equinovarus, or clubfoot, is a common developmental disorder of the foot, affecting at least 2 in every 1000 live births in Scotland. The defect is characterised by a twisting of the foot and loss of calf muscle. Diagnosis is usually made on postnatal examination and treatment; usually a series of foot manipulations, takes place within the first year. Treatment can be particularly painful and is not always successful as the defect can recur leading to life-long disability in some cases. Very little is known of the aetiology of clubfoot despite it being such a common problem and therefore our lab set out to elucidate the developmental processes that occur during limb development which result in clubfoot. The chick limb is a well established model system used to study many developmental processes, signalling events and has been used to model several human limb disorders. We have developed a chick model of human clubfoot using a neuromuscular paralysing agent, resulting in a range of clubfoot conditions. Our lab is currently using this chick model to determine the developmental basis of the disorder. Initial phenotypic analyses of the chick clubfoot limb correlate well with those observed in human clubfoot; both exhibit muscle loss, tendon problems and bony abnormalities. We will use this chick model of human clubfoot to test our hypothesis that clubfoot may result from a failure of hindlimb rotation and elucidate the developmental and molecular basis of this congenital defect.