The identification of genes involved in mammalian craniofacial development and disease

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Birth defects arising from abnormal development of the embryo are a major cause of infant mortality and childhood disabilities. On average 3-4% of liveborn babies have a major congenital abnormality, and of the 15-20% of pregnancies which spontaneously abort, many are due to chromosomal or other developmental anomalies. A common feature of many developmental disorders is dysmorphology of the face, suggesting that genes important in patterning the face are also important in the development of other organ systems. During development of the embryo many of the features of the face derive from a series of swellings termed the pharyngeal arches. The complex processes which determine how the face develops are in a large part controlled by the co-ordinated expression of a large number of genes in the first two of the five pharyngeal arch pairs. While we know some of the genes involved in these processes, the precise mechanisms of craniofacial development are relatively poorly understood. In this project we propose a large scale approach to identifying genes involved in development of the mammalian face and to further delineating their role in development and human disease. This approach takes advantage of state of the art genomic technologies available at the IMB and through existing collaborations overseas. In collaboration with Dr Bento Soares (University of Iowa) we have constructed a library containing all of the genes which are expressed in the first two pairs of pharyngeal arches in the developing mouse embryo. Using an approach designed to eliminate all those genes which are expressed in all or most tissues of the body and play a general role in the body's metabolism, we will select for those genes which play a specific and important role in embryonic development. We will then isolate the human counterparts of these genes and more thoroughly investigate their role in embryonic development and disease.