Future directions: molecular approaches provide insights into palatal clefting and repair

Abstract

Normal development of the palate depends on spatial and temporal coordination of complex cellular processes and tissue-tissue interactions. Because these processes are quite sensitive to environmental and genetic perturbation, clefts of the palate are among the most common congenital anomalies seen in live births. The clinical burden of cleft palate is significant, as conventional treatments include surgical repair combined with long-term rehabilitation. Affected children may require multiple operations and often have secondary problems such as perturbed speech development, dental occlusion, maxillary growth deficiencies and otitis media. Recent reports, from patient studies and mouse models, have implicated a number of genes in palatogenesis. It is difficult to pinpoint the direct pathological effects of specific genes in humans; therefore, the majority of mechanistic insights have derived from murine models. Furthermore, recent technological advances have made mice an ideal system for studying the signalling events associated with cleft palate. This review discusses several illustrative examples of genetic or molecular studies in which in utero reversal of cleft palate reveals sequential requirements in palate formation. As we develop a more comprehensive understanding of the genetic mechanisms underlying normal and pathological palate development, we can begin to consider the possibility of molecular tools to complement or even replace surgical interventions.