title: BMP signals regulate Dlx5 during early avian skull development.
abstract: The vertebrate skull vault forms almost entirely by the direct mineralisation of mesenchyme, without the formation of a cartilaginous template, a mechanism called membranous ossification. Dlx5 gene mutation leads to cranial dismorphogenesis which differs from the previously studied craniosynostosis syndromes [Development 126 (1999), 3795; Development 126 (1999), 3831]. In avians, little is known about the genetic regulation of cranial vault development. In this study, we analyze Dlx5 expression and regulation during skull formation in the chick embryo. We compare Dlx5 expression pattern with that of several genes involved in mouse cranial suture regulation. This provides an initial description of the expression in the developing skull of the genes encoding the secreted molecules BMP 2, BMP 4, BMP 7, the transmembrane FGF receptors FGFR 1, FGFR 2, FGFR 4, the transcription factors Msx1, Msx2, and Twist, as well as Goosecoid and the early membranous bone differentiation marker osteopontin. We show that Dlx5 is activated in proliferating osteoblast precursors, before osteoblast differentiation. High levels of Dlx5 transcripts are observed at the osteogenic fronts (OFs) and at the edges of the suture mesenchyme, but not in the suture itself. Dlx5 expression is initiated in areas where Bmp4 and Bmp7 genes become coexpressed. In a calvarial explant culture system, Dlx5 transcription is upregulated by BMPs and inhibited by the BMP-antagonist Noggin. In addition, FGF4 activates Bmp4 but not Bmp7 gene transcription and is not sufficient to induce ectopic Dlx5 expression in the immature calvarial mesenchyme. From these data, we propose a model for the regulatory network implicated in early steps of chick calvarial development.
authors.affiliation: Institut d'Embryologie Cellulaire et Moléculaire, CNRS, UMR 7128, 49 bis, avenue de La Belle Gabrielle, 94736, Nogent-sur-Marne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Holleville
authors.forename: Alexandra
authors.initials: A
authors.lastname: Quilhac
authors.forename: Martine
authors.initials: M
authors.lastname: Bontoux
authors.forename: Anne Hélène
authors.initials: AH
authors.lastname: Monsoro-Burq
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002642:Chick Embryo; D005346:Fibroblast Growth Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000378:metabolism*; D051957:MSX1 Transcription Factor; D008648:Mesoderm / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D012886:Skull / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C501120:Dlx5 protein, mouse; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D005346:Fibroblast Growth Factors