Ectodermally derived FGF8 defines the maxillomandibular region in the early chick embryo: Epithelial-mesenchymal interactions in the specification ofthe craniofacial ectomesenchyme

The most rostral cephalic crest cells in the chick embryo first populate ub iquitously in the rostroventral head. Before the influx of crest cells, the ventral head ectoderm expresses Fgf8 in two domains that correspond to the future mandibular arch. Bmp4 is expressed rostral and caudal to these doma ins. The rostral part of the Bmp4 domain develops into the rostral end of t he maxillary process that corresponds to the transition between the maxillo mandibular and premandibular regions. Thus, the distribution patterns of EG F8 and BMP4 appear to foreshadow the maxillomandibular region in the head e ctoderm. In the ectomesenchyme of the pharyngula embryo, expression pattern s of some homeobox genes overlap the distribution of their upstream growth factors. Dlx1 and Barx1, the targets of FGF8, are expressed in the mandibul ar ectomesenchyme, and Msx1, the target of BMP4, in its distal regions. Ect opic applications of FGF8 lead to shifted expression of the target genes as well as repatterning of the craniofacial primordia and of the trigeminal n erve branches. focal injection of a lipophilic dye, DiI, showed that this s hift was at least in part due to the posterior transformation of the origin al premandibular ectomesenchyme into the mandible, caused by the changed di stribution of FGF8 that defines the mandibular region. We conclude that FGF 8 in the early ectoderm defines the maxillomandibular region of the prephar yngula embryo, through epithelial-mesenchymal interactions and subsequent u pregulation of homeobox genes in the local mesenchyme. BMP4 in the ventral ectoderm appears to limit the anterior expression of Fgf8. Ectopic applicat ion of BMP4 consistently diminished part of the mandibular arch. (C) 2000 A cademic Press.