부산대학교 도서관

The development of the craniofacial skeleton relies on complex temporospatial organization of diverse cell types by key signalling molecules. Even minor disruptions to these processes can result in deleterious consequences for the structure and function of the skull. Thyroid hormone deficiency causes delayed craniofacial and tooth development, dysplastic facial features and delayed development of the ossicles in the middle ear. Thyroid hormone excess, by contrast, accelerates development of the skull and, in severe cases, might lead to craniosynostosis with neurological sequelae and facial hypoplasia. The pathogenesis of these important abnormalities remains poorly understood and underinvestigated. The orchestration of craniofacial development and regulation of suture and synchondrosis growth is dependent on several critical signalling pathways. The underlying mechanisms by which these key pathways regulate craniofacial growth and maturation are largely unclear, but studies of single-gene disorders resulting in craniofacial malformations have identified a number of critical signalling molecules and receptors. The craniofacial consequences resulting from gain-of-function and loss-of-function mutations affecting insulin-like growth factor 1, fibroblast growth factor receptor and WNT signalling are similar to the effects of altered thyroid status and mutations affecting thyroid hormone action, suggesting that these critical pathways interact in the regulation of craniofacial development. This article discusses the role of thyroid hormones in craniofacial bone formation. The clinical consequences of thyroid hormone excess and deficiency are also outlined. Key points Thyroid hormone deficiency during development results in delayed intramembranous and endochondral ossification in the skull, which manifests as patent or persistent fontanelles, patent sutures, delayed dentition, wormian bones and deafness. Thyroid hormone excess during development results in advanced intramembranous and endochondral ossification in the skull, which manifests as premature fusion of the calvarial sutures and cranial base synchondroses. These characteristic craniofacial malformations indicate that thyroid hormones have a pivotal role in development and growth of the craniofacial skeleton and demonstrate that the skull is exquisitely sensitive to changes in thyroid status. Thyroid hormone-induced changes in fibroblast growth factor receptor, insulin-like growth factor 1 and WNT signalling in osteoblasts and chondrocytes indicate that these pathways are intricately involved in the regulation of craniofacial development by T.sub.3.
Author(s): Victoria D. Leitch [sup.1] [sup.2] , J. H. Duncan Bassett [sup.1] , Graham R. Williams [sup.1] Author Affiliations: (1) Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial [...]