Head Development: Genetic Determinants and Tissue Potency

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Congenital malformations involving major defects of brain (anencephalus and related anomalies) and facial structures (ear, face and neck) are encountered in 3.4 and 1.4 per 10000 births respectively (Congenital Malformations Australia 1981-1996, National Perinatal Statistics Unit) and they constitute a substantial clinical burden. It is believed that these major structural defects usually result from abnormal development in the first trimester, which coincides with the time frame for the formation of the basic components of the embryonic head in the mouse. Knowledge of the formation of the head in the mouse model is therefore relevant to the understanding of related developmental processes in early human development. This project which involves the application of sophisticated embryological and molecular analyses on mouse embryos generated by transgenesis and genetic manipulation provides a detailed studies of craniofacial morphogenesis in a mammalian model for early human development. The micro-manipulation procedures, embryo culture, fluorescence microscopy and the in situ hybridization are routinely performed in our laboratory, and most of the mouse lines are well established in my laboratory. Experiments proposed for this project that focus on the embryological and molecular analysis of normal and mutant embryos should discover new information on the cellular and molecular mechanisms that regulate head development. The knowledge will also offer insight into the pathogenesis of similar craniofacial malformations in other mutant embryos.