Cellular and developmental basis of orofacial clefts.

During craniofacial development, defective growth and fusion of the upper lip and/or palate can cause orofacial clefts (OFCs), which are among the most common structural birth defects in humans. The developmental basis of OFCs includes morphogenesis of the upper lip, primary palate, secondary palate, and other orofacial structures, each consisting of diverse cell types originating from all three germ layers: the ectoderm, mesoderm, and endoderm. Cranial neural crest cells and orofacial epithelial cells are two major cell types that interact with various cell lineages and play key roles in orofacial development. The cellular basis of OFCs involves defective execution in any one or several of the following processes: neural crest induction, epithelial-mesenchymal transition, migration, proliferation, differentiation, apoptosis, primary cilia formation and its signaling transduction, epithelial seam formation and disappearance, periderm formation and peeling, convergence and extrusion of palatal epithelial seam cells, cell adhesion, cytoskeleton dynamics, and extracellular matrix function. The latest cellular and developmental findings may provide a basis for better understanding of the underlying genetic, epigenetic, environmental, and molecular mechanisms of OFCs.