Molecular mechanisms in calvarial bone and suture development, and their relation to craniosynostosis.
The development and growth of the skull is a co-ordinated process involving many different tissues that interact with each other to form a complex end result. When normal development is disrupted, debilitating pathological conditions, such as craniosynostosis (premature calvarial suture fusion) and cleidocranial dysplasia (delayed suture closure), can result. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3(FGFR1, 2, and 3), as well as the transcription factors MSX2 and TWIST cause craniosynostosis, and that mutations in the transcription factor RUNX2 (CBFA1) cause cleidocranial dysplasia. However, relatively little is known about the development of the calvaria: where and when these genes are active during normal calvarial development, how these genes may interact in the developing calvaria, and the disturbances that may occur to cause these disorders. In this work an attempt has been made to address some of these questions from a basic biological perspective. The expression patterns of the above-mentioned genes in the developing mouse skull are detailed. The microdissection and in vitro culture techniques have begun the task of identifying Fgfrs, Msx2, and Twist interacting in intricate signalling pathways that if disrupted could lead to craniosynostosis.
Developmental Biology Programme, Institute of Biotechnology, and Department of Pedodontics and Orthodontics, Institute of Dentistry, University of Helsinki, Finland.
David P C
DP
Rice
Ritva
R
Rice
Irma
I
Thesleff
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit; D003393:Cranial Sutures / Q000196:embryology*; D003398:Craniosynostoses / Q000196:embryology / Q000235:genetics*; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D058574:Integrin-Binding Sialoprotein; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012886:Skull / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1
D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; C084119:MSX2 protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3