Clubfoot is a developmental defect of the lower limb that affects as many as 1 in 500 births across Scotland (Miedzybrodzka., 2003). How the clubfoot defect arises during embryonic development is not known, although a number of tissue abnormalities have been postulated to be the primary abnormality in the development of the clubfoot defect. A chick model of clubfoot was created to investigate the developmental basis of clubfoot. Using a method modified from previous work carried out by Germiller and co-workers (1998), clubfoot was induced in the chick embryo using the pharmacological agent decamethonium bromide. The defect was confirmed to be clubfoot by comparing the features observed in the chick hindlimb with characteristic features observed in human clubfoot. By analysing the development of the hindlimb muscle, nerves, skeleton, tendons and vasculature the primary defect was found to be a loss of muscle in the hindlimb resulting from both an increase in apoptosis and a decrease in muscle differentiation. This resulted in a loss of muscle-nerve branches, which were found to regress in the absence of muscle, and tendons which were either missing or abnormally positioned. The vasculature in the clubfoot limb appeared grossly normal. A number of environmental causes of clubfoot cause a compression of the developing embryo, for example a reduction in the volume of amniotic fluid surrounding the embryo, physically compresses and immobilises the embryo. To investigate this, the amniotic fluid was removed from around chick embryos and was found to cause clubfoot. The primary abnormality was found to be a loss of muscle in the hindlimb. Thus, it has been demonstrated that clubfoot, induced both pharmacologically and physically, results primarily from a loss of muscle in the hindlimb. During embryonic development, the hindlimbs are required to rotate. It was found that this process was disrupted in chick clubfoot providing evidence for the long-standing theory (Bohm., 1929) that disrupted hindlimb rotation may underlie clubfoot. It is suggested from the data in this study, that a loss of hindlimb muscle disrupts the process of rotation and thus the feet remain unrotated, resulting in clubfoot.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:542633 |
| Date | January 2011 |
| Creators | Kilby, Elizabeth Louise |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=166649 |
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