Cleft lip∕palate. From embryology to developmental pathogenesis

Cleft of the lip associated with or unassociated with cleft of the palate and cleft palate (CLP) represent frequent birth defects, and the mechanisms by which they occur are not completely clear. On the other hand, knowledge of the normal mechanisms underlying lip development and palatogenesis is still incomplete, and therefore a better understanding and consolidation of our knowledge in this field could help to study these deformities. Upper lip and secondary palate formation are complex processes, involving the subtle integration of several biological events, the disruption of which causes the clefting phenotype. Indeed, these developmental events imply a series of morphogenetic changes involving concerted cell survival, migration, growth, pattern generation, modulation of adhesiveness, death and differentiation. In recent years, genetically engineered animal models and in vitro palate cultures have greatly advanced our knowledge of the cellular and molecular pathways underlying normal orofacial morphogenesis, and abnormally developed CLP as well. Indeed, most of the morphogenetic events of craniofacial development are highly conserved amongst vertebrates, therefore animal models have revealed major insights into the mechanisms that take place in human orofacial development. Given their complexity, it is easy to imagine that the failure of the highly coordinated processes that guide the union of the lip and palate causes various forms of clefts. This article provides an overview of the embryological development of the lip and secondary palate, as well as the mechanisms underlying deviant development resulting in CLP, concentrating on the cellular and molecular characteristics.