Cellular and Molecular Mechanisms of Palatogenesis

Palatogenesis involves the initiation, growth, morphogenesis, and fusion of the primary and secondary palatal shelves from initially separate facial prominences during embryogenesis to form the intact palate separating the oral cavity from the nostrils. The palatal shelves consist mainly of cranial neural crest-derived mesenchymal cells covered by a simple embryonic epithelium. The growth and patterning of the palatal shelves are controlled by reciprocal epithelial-mesenchymal interactions regulated by multiple signaling pathways and transcription factors. During palatal shelf outgrowth, the embryonic epithelium develops a "teflon" coat consisting of a single, continuous layer of periderm cells that prevents the facial prominences and palatal shelves from forming aberrant interepithelial adhesions. Palatal fusion involves not only spatiotemporally regulated disruption of the periderm but also dynamic cellular and molecular processes that result in adhesion and intercalation of the palatal medial edge epithelia to form an intershelf epithelial seam, and subsequent dissolution of the epithelial seam to form the intact roof of the oral cavity. The complexity of regulation of these morphogenetic processes is reflected by the common occurrence of cleft palate in humans. This review will summarize major recent advances and discuss major remaining gaps in the understanding of cellular and molecular mechanisms controlling palatogenesis.