BMP signals regulate Dlx5 during early avian skull development

• Published in: Developmental biology 2003-05, Vol.257 (1), p.177-189
• Main Authors: Holleville, Nicolas, Quilhac, Alexandra, Bontoux, Martine, Monsoro-Burq, Anne-H.élène
• Format: Article
• Language: English
• Subjects: Animals; BMP; Bone Morphogenetic Proteins; Bone Morphogenetic Proteins - metabolism; Cell Division; Cell Division - physiology; Chick Embryo; Dlx5; FGF4; FGFR; Fibroblast Growth Factors; Fibroblast Growth Factors - metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; Goosecoid; Goosecoid Protein; Homeodomain Proteins; Homeodomain Proteins - metabolism; Intramembranous ossification; Life Sciences; Mesoderm; Mesoderm - metabolism; Msx1; MSX1 Transcription Factor; Noggin; Osteoblasts; Osteoblasts - metabolism; Repressor Proteins; Signal Transduction; Signal Transduction - physiology; Skull; Skull - embryology; Transcription Factors; Transcription Factors - metabolism
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/S0012-1606(03)00059-9

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.