Mandibular morphogenesis and craniofacial malformations.

Four questions have been addressed in this review. What is morphogenesis? I conclude that morphogenesis is simply development or change of shape and distinguish morphogenesis both from differentiation and from growth, although predominant growth along one axis can alter shape. Morphogenesis can be considered at all levels from the molecule to the population. I concentrated on cells, tissues, and organs. How does the mandible develop? A brief overview of the origin, migration, and differentiation of the neural crest and other cells which constitute the mandible has been provided. How is mandibular morphogenesis controlled? Several lines of evidence are presented to show that basic elements of morphogenesis, eg number and shape of skeletal elements in the mandible, are a property possessed by the mesenchymal cells which will form those tissues, before they differentiate into cartilage or bone. Reaggregated mesenchymal cells form site-specific-shaped cartilages. First arch neural crest, transplanted to sites of presumptive second and third arch neural crest, migrates to the second arch region but forms first branchial arch skeletal and muscle elements in that ectopic site. Morphogenesis is an intrinsic property of the neural crest and of the mesenchymal cells which arise from the crest. What is the developmental basis of craniofacial malformations? Evidence is presented to show that defects at any stage of mandibular development can lead to craniofacial malformations. Absence of the neural crest, abnormal migration of neural crest-derived cells, abnormal extracellular environments, defective interactions between or differentiation of mesenchymal cells, altered inductive tissue interactions, and deficiencies in epigenetic interactions between components of the mandible can all lead to craniofacial malformations. The challenge for the clinical and basic craniofacial biologist is to identify the defective cellular process which has produced the malformation and to devise preventative or corrective procedures which restore that process to normality.