title: Temporospatial cell interactions regulating mandibular and maxillary arch patterning.
abstract: The cellular origin of the instructive information for hard tissue patterning of the jaws has been the subject of a long-standing controversy. Are the cranial neural crest cells prepatterned or does the epithelium pattern a developmentally uncommitted population of ectomesenchymal cells? In order to understand more about how orofacial patterning is controlled we have investigated the temporal signalling interactions and responses between epithelium and mesenchymal cells in the mandibular and maxillary primordia. We show that within the mandibular arch, homeobox genes that are expressed in different proximodistal spatial domains corresponding to presumptive molar and incisor ectomesenchymal cells are induced by signals from the oral epithelium. In mouse, prior to E10, all ectomesenchyme cells in the mandibular arch are equally responsive to epithelial signals such as Fgf8, indicating that there is no pre-specification of these cells into different populations and suggesting that patterning of the hard tissues of the mandible is instructed by the epithelium. By E10.5, ectomesenchymal cell gene expression domains are still dependent on epithelial signals but have become fixed and ectopic expression cannot be induced. At E11 expression becomes independent of epithelial signals such that removal of the epithelium does not affect spatial ectomesenchymal expression. Significantly, however, the response of ectomesenchyme cells to epithelial regulatory signals was found to be different in the mandibular and maxillary primordium. Thus, whereas both mandibular and maxillary arch epithelia could induce Dlx2 and Dlx5 expression in the mandible and Dlx2 expression in the maxilla, neither could induce Dlx5 expression in the maxilla. Reciprocal cell transplantations between mandibular and maxillary arch ectomesenchymal cells revealed intrinsic differences between these populations of cranial neural crest-derived cells. Research in odontogenesis has shown that the oral epithelium of the mandibular and maxillary primordia has unique instructive signaling properties required to direct odontogenesis, which are not found in other branchial arch epithelia. As a consequence, development of jaw-specific skeletal structures may require some prespecification of maxillary ectomesenchyme to restrict the instructive influence of the epithelial signals and allow development of maxillary structures distinct from mandibular structures.
authors.affiliation: Department of Craniofacial Development, GKT Dental Institute, Kings College, Guy's Hospital, London SE1 9RT, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Ferguson
authors.forename: A S
authors.initials: AS
authors.lastname: Tucker
authors.forename: P T
authors.initials: PT
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D017690:Cell Transplantation; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D005314:Embryonic and Fetal Development; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D007568:Jaw / Q000196:embryology*; D051957:MSX1 Transcription Factor; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C095587:Barx1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C088334:Distal-less homeobox proteins; C501120:Dlx5 protein, mouse; C496457:Fgf8 protein, mouse; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D016601:RNA-Binding Proteins; C093661:Tes protein, mouse; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors