European Cells and Materials Vol. 14. Suppl.

2, 2007 (page 15)

ISSN 1473-2262

NORMAL AND ABNORMAL LOWER JAW DEVELOPMENT

T. Peltomki Clinic for Orthodontics and Pediatric Dentistry, Center for Dental and Oral Medicine, University of Zurich, Switzerland
Functioning of the masticatory and breathing apparatus and harmony of the face are significantly influenced by the size and shape of the lower jaw. Absent or deficient lower jaw growth may lead to life threatening condition because of obstruction in the airway. Prevention and treatment of congenital and acquired mandibular anomalies necessitate understanding of mandibular morphogenesis at the cellular and molecular level. Mandibular development is complex and peculiar, since it involves three different and essential elements: Meckels cartilage, intramembraneous bony component and cartilaginous condylar blastema.1 Meckels cartilage is thought to be the supportive element of the first branchial arch, however, it may have a crucial role as an inductor for the intramembraneous bone formation of the mandible on its lateral surface. 2 Thus, defect in the neural crest originating Meckels cartilage may adversely affect jaw morphogenesis. A more serious defect has been documented following FGF8 gene inactivation: the first branchial arch does not develop properly and mandible remains rudimentary. 3 Genetic experiments in mice have begun to address the role of epithelial-mesenchymal interactions by targeting genes expressed in one tissue layer. It has been shown that Tgfb, Pitx1, Tbx1, Sox9, and Runx2 are necessary for normal lower jaw growth and development.4-7 Condylar cartilaginous blastema appears later in the development than primary cartilages. Ihh seems to be very important for the development of the this secondary cartilage and the TMJ.8 During development the anteriorly expanding cartilaginous blastema fuses with the posteriorly growing bony part, however, process of fusion and defects in this are poorly understood. CTs of patients with hemifacial microsomia have revealed a small bony structure on the buccal side of the mandible not being attached to the ramus.9 This structure could be condylar blastema, which did not fuse to the mandibular ramus. During postnatal growth condylar cartilage has a central role in the mandibular growth. Recent studies have increased our understanding on the endochondral bone formation cascade in the condylar cartilage. Large variation in the growth quantity and direction of condylar growth leads to large individual variation in the mandibular shape and also to difference in response to treatment. A recent association study has shown that the variation may be partly due to single nucleotide polymorphism in the growth hormone receptor gene.10 Holistic view of the factors associated with preand postnatal mandibular growth is poorly understood and the future challenge is to disclose these factors to prevent and treat individuals with lower jaw growth disturbances. REFERENCES: 1 S.K. Lee et al., (2001) Prenatal development of the human mandible. Anat Record 263:314-25. 2 J. Frommer and M.R. Margolies (1971) Contribution of Meckels cartilage to ossification of the mandible in mice. J Dent Res 50:1260-7. 3 A. Trumpp et al. (1999) Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Gen Dev 13:3136-48. 4 C. Lanctt et al., (1999) Hindlimb patterning and mandible development require the Ptx1 gene. Development 126: 1805-10. 5 P. Miettinen et al., (1999) EGFR function is necessary for normal craniofacial development and palate closure. Nature Genet 22:69-73. 6 I. Satokata et al., (2000) Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nature Genet 24:391-5. 7 H. Wurdak et al., (2006) DiGeorge syndrome and pharyngeal apparatus development. BioEssays 28:1078-86. 8 Y. Shibukawa et al. (2007) TMJ formation and condyle growth require Ihh signaling. Dev Dyn 236:426-34. 9 C.E. Huisinga-Fischer et al., (2003) Longitudinal results of mandibular distraction osteogenesis in hemifacial microsomia. J Craniofac Surg 14:924-33. 10 J. Zhou et al., (2005) The GHR gene is associated with mandibular height in a Chinese population J Dent Res 84:1052-6.