Congenital craniofacial malformations can be caused by a large number of factors; genetic, environmental or the interplay of both. Recent progress in linkage analyses and positional cloning have identified many genetic mutations associated with human craniofacial syndromes. However, the mechanisms of how such mutations in a gene result in an altered phenotype require the molecular dissection of the signal transduction pathway in tissues and cells that are elements of craniofacial development. We are particularly interested in skeletogenesis since 25% of all congenital malformations involve the skeleton. We have initiated 5 subtopics focussing on the different aspects of skeletogenesis, including transcriptional control of chondrogenesis, cell adhesion and cytoskeletal signal transduction in chondrocyte differentiation, cranial neural crest cell migration and differentiation, differentiative pathway of osteo-chondro-progenitor cells under compressive force and the generation of monoclonal antibodies against stage specific chondrocyte markers. These subtopics are independent areas of research, yet collectively are interrelated scientifically and technically to address some of the key questions in the field of craniofacial development. It is our goal that through these subtopics, we will be able to identify signal transduction pathways elicited by intrinsic factors such as transcriptional activation, and extrinsic factors such as cell-cell interactions and cell-substrate interactions, leading to early events of chondrogenesis. We will also extrapolate our knowledge of normal chondrogenesis to elucidate the etiology of various forms of genetic diseases and disorders of the cartilage, for the development of preventive, diagnostic and therapeutic strategies.
