Making faces: neural crest cells in craniofacial development and congenital birth defects such as Treacher Collins syndrome

Abstract

Craniofacial anomalies account for approximately one-third of congenital defects. The majority of bone, cartilage and connective tissue in the head and face are derived from neural crest cells. Consequently, defects in neural crest cell patterning are thought to underlie most craniofacial anomalies. Understanding the etiology and pathogenesis of craniofacial anomalies is dependent upon a thorough knowledge of the mechanisms that govern neural crest cell development. Treacher Collins syndrome (TCS) which is characterised by hypoplasia of the facial bones, is caused by mutations in TCOF1 and deficiencies in the number of migrating neural crest cells and their proliferative capacity. We are investigating the function of Tcof1 in neural crest cells in connection with its role in TCS. Haploinsufficiency of Tcof1 affects ribosome biogenesis as well as cell proliferation and survival, however, inhibition of apoptosis is sufficient to prevent the manifestation of craniofacial anomalies characteristic of TCS. Our work therefore is facilitating the development of therapeutic approaches to prevent the pathogenesis of craniofacial malformation syndromes, which has broad implications for other congenital birth defects of similar etiology to TCS. This research was supported by March of Dimes grants FY05-82 and FY08-265 and the National Institute of Dental and Craniofacial Research DE016082-06