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 complet e. The identification of heterozygous mutations in FGFR1, -2 and -3 and TWI ST as well as microdeletions of TWIST in human craniosynostosis syndromes h as highlighted these genes as playing important roles in maintaining the su ture as a growth centre. In contrast to Drosophila, a molecular relationshi p between human (or other vertebrate) TWIST and FGFR genes has not yet been established TWIST mutations exert their effect via haploinsufficiency wher eas FGFR mutations have a gain-of-function mechanism of action. To investig ate the biological basis of FGFR signalling pathways in the developing calv arium 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) T wist expression precedes that of Fgfr genes at the time of initiation of th e coronal suture; (2) in contrast to Fgfr transcripts, which are localised within and around the developing bone domains, Twist is expressed by the mi dsutural mesenchyme cells. Twist expression domains show some overlap with those of Fgfr2, which is expressed in the most immature (proliferating) ost eogenic tissue. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.