In this application, we propose to integrate our research in functional genomics and craniofacial morphology/dysmorphology within the FaceBase Consortium. Specifically, we will focus on the development of the mandible and maxilla. Congenital malformations involving these facial bones significantly impact quality of life because our face is our identity. For example, mandibular dysmorphogenesis ranging from agenesis of the jaw to micrognathia is a common malformation and appears in multiple syndromes. Micrognathia not only presents as a facial deformity but can also cause cleft palate and airway obstruction, such as in Pierre-Robin sequence. The maxilla contributes to mid-facial formation. Maxillary hypoplasia is often associated with cleft palate and has been described in more than sixty different syndromes. Despite their importance, the mechanisms that regulate facial bone development are relatively uncharacterized. This is a significant gap in our knowledge and an important opportunity to generate invaluable resources for the research community. The proposed work is a logical progression from our current spoke project within the FaceBase Consortium on palatal development. Over the past five years, we have deposited nearly 200 hard and soft tissue scans and 125 microarray gene expression datasets in the FaceBase hub. These datasets have demonstrated their utility, as shown by other researchers presentations at major international conferences and publications. Equally importantly, our team has played a significant role in the FaceBase Consortium, the hub website design, data organization and presentation. Building on our experience and in alignment with RFA-DE-14-004, we propose to investigate facial bone development and malformations.
In Specific Aim 1, we will perform global and specific gene expression profiling analysis of mandible development, and will integrate these datasets with cell lineage and 3D dynamic imaging analyses. In collaboration with the ontology group within the FaceBase consortium, we will define anatomical landmarks and morphometric parameters of the developing mandible.
In Specific Aim 2, we will expand our gene expression profile analyses in the developing maxilla. We will correlate this information with 3D imaging of the maxilla and define anatomical landmarks and parameters in collaboration with the ontology group within the FaceBase consortium. Our data will facilitate the investigation of the molecular regulatory mechanism of facial bone formation. This study will showcase how our datasets at the hub can facilitate the generation of hypothesis-driven research and collaborations. Because of the prevalence of facial bone defects in orofacial clefting patients and the lack of quantitative studies in this area, our proposed study will fill a void and provide a significant resource for the research community.
Congenital malformations involving the facial bones significantly impact quality of life because our face is our identity, but little is known about how the molecular mechanisms that regulate the normal and abnormal development of these bones. We will study the development of the mandible and maxilla through gene expression profiling and quantitative 3D dynamic imaging analyses. Our study will generate important resources for the research community, inform clinical diagnosis and provide potential approaches to prevent craniofacial malformations.