To Stick or Not to Stick: Adhesions in Orofacial Clefts

SIMPLE SUMMARY: During embryonic development, cells proliferate and move to form structures essential to each organ. As these dynamic processes occur cells must form adhesions with their neighbors. These adhesions serve as communication centers to amplify the behavior of individual cells into collective cellular events. Here, we review cell-to-cell adhesions and focus on their role in the development of the face and palate. ABSTRACT: Morphogenesis requires a tight coordination between mechanical forces and biochemical signals to inform individual cellular behavior. For these developmental processes to happen correctly the organism requires precise spatial and temporal coordination of the adhesion, migration, growth, differentiation, and apoptosis of cells originating from the three key embryonic layers, namely the ectoderm, mesoderm, and endoderm. The cytoskeleton and its remodeling are essential to organize and amplify many of the signaling pathways required for proper morphogenesis. In particular, the interaction of the cell junctions with the cytoskeleton functions to amplify the behavior of individual cells into collective events that are critical for development. In this review we summarize the key morphogenic events that occur during the formation of the face and the palate, as well as the protein complexes required for cell-to-cell adhesions. We then integrate the current knowledge into a comprehensive review of how mutations in cell-to-cell adhesion genes lead to abnormal craniofacial development, with a particular focus on cleft lip with or without cleft palate.