Genetics and morphology of the middle ear ossicles in the developing mouse embryo

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I am interested in researching how the middle ear ossicles develop. Defects in these ossicles, such as fusion, are fairly common and lead to hearing problems. These defects can be seen by using CT (computed tomography) scans, which allow assessment of the patient s suitability for corrective ear surgery. The middle ear is composed of three ossicles that form a chain linking the ear drum with the inner ear. The three ossicles are connected by joints, which can be malformed or absent, resulting in fusion of the middle ear and hearing loss. In these patients it is unclear how the defects observed arose. This is due to a lack of information available with respect to formation of these joints during normal development.This research attempts to correct this deficit in our knowledge by investigating the middle ear, first in normal and then in mutant mouse embryos. Development of the mouse middle ear has been shown to be similar to that of humans and therefore information obtained from using mouse models can be directly related to human patients. I plan to concentrate mainly on the first two ossicles and joint region, as this is the region where defects most often occur. We would first like to know: sum How the joint forms sum What genes are involved in joint formation sum How is the position of the joint determined sum How do each of the three ossicles develop their individual specification (ie their difference from each other) during normal embryonic development.Having identifies how this region of the middle ear normally forms we will use this information to investigate cases where there is an abnormality. For this we will be analysing a mouse embryo that has a mutation in a gene called TCOF1. Patients with defects in this gene develop Treacher Collins syndrome (TCS) which is associated with a fused middle ear and hearing loss in almost 100% of cases. This work should give a clear picture of how the middle ear defects seen in TCS occur during embryology. Ultimately, such information may help patients with TCS by allowing for a more informed decision when the option for surgery is discussed.