Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for twist in suture initiation and biogenesis.
Sutural growth depends on maintenance of a balance between proliferation of osteogenic stem cells and their differentiation to form new bone, so that the stem cell population is maintained until growth of the skull is complete. The identification of heterozygous mutations in FGFR1, -2 and -3 and TWIST as well as microdeletions of TWIST in human craniosynostosis syndromes has highlighted these genes as playing important roles in maintaining the suture as a growth centre. In contrast to Drosophila, a molecular relationship between human (or other vertebrate) TWIST and FGFR genes has not yet been established. TWIST mutations exert their effect via haploinsufficiency whereas FGFR mutations have a gain-of-function mechanism of action. To investigate the biological basis of FGFR signalling pathways in the developing calvarium we compared the expression patterns of Twist with those of Fgfr1, -2 and -3 in the fetal mouse coronal suture over the course of embryonic days 14-18, as the suture is initiated and matures. Our results show that: (1) Twist expression precedes that of Fgfr genes at the time of initiation of the coronal suture; (2) in contrast to Fgfr transcripts, which are localised within and around the developing bone domains, Twist is expressed by the midsutural mesenchyme cells. Twist expression domains show some overlap with those of Fgfr2, which is expressed in the most immature (proliferating) osteogenic tissue.
Johnson
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Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Iseki
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Wilkie
A O
AO
Morriss-Kay
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GM
D000818:Animals; D003393:Cranial Sutures / Q000196:embryology*; D005314:Embryonic and Fetal Development; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; 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*; D014157:Transcription Factors; D051879:Twist-Related Protein 1
D009687:Nuclear Proteins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D051879:Twist-Related Protein 1; 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