Suture biology: Lessons from molecular genetics of craniosynostosis syndromes.

Sutures are critical growth sites in the developing craniofacial skeleton, and equally importantly, they are the target tissues for certain orthodontic therapeutic modalities. For these reasons, suture biology has long been an area of significant interest in orthodontics. In fact, much of our knowledge on sutures, such as structure, ontogeny, growth and development, pathology, and tissue response to biomechanical forces, is based on investigations conducted by orthodontic researchers in the 1950-1970s. Despite their significant impact in the establishment of the current paradigm in suture biology, these earlier studies have not provided much information on the molecular and cellular mechanisms of suture development. Only in the last 5 or 6 years, identification of genes involved in genetic disorders of premature suture closure (syndromes of craniosynostosis) has uncovered the first clues to some key molecules and their specific roles in this process. The list, which is expected to get longer, includes fibroblast growth factor receptors (FGFRs), MSX2, and TWIST. FGFRs belong to a family of cell membrane receptor kinases and bind to their principal ligands, fibroblast growth factors (FGFs). Upon binding to FGFs, FGFRs transduce intracellular signaling cascades and ultimately modify cellular behavior, such as cell proliferation and differentiation. MSX2 and TWIST are transcription factors that bind to regulatory regions of target effector genes and determine their expression. In addition to the above-mentioned molecules, recent tissue recombination and biochemical studies have added FGFs and transforming growth factors to the list of key molecules in suture biogenesis. The purpose of this article is not to reiterate the earlier classical studies, which have been extensively reviewed by others, but to present the new and exciting developments in the field of suture research at the genetic and cellular levels. These new perspectives and what lies ahead as future challenges in this field are discussed.