title: Sonic hedgehog from pharyngeal arch 1 epithelium is necessary for early mandibular arch cell survival and later cartilage condensation differentiation.
abstract: BACKGROUND
  Morphogenesis of vertebrate craniofacial skeletal elements is dependent on a key cell population, the cranial neural crest cells (NCC). Cranial NCC are formed dorsally in the cranial neural tube and migrate ventrally to form craniofacial skeletal elements as well as other tissues. Multiple extracellular signaling pathways regulate the migration, survival, proliferation, and differentiation of NCC.
  
  
  RESULTS
  In this study, we demonstrate that Shh expression in the oral ectoderm and pharyngeal endoderm is essential for mandibular development. We show that a loss of Shh in these domains results in increased mesenchymal cell death in pharyngeal arch 1 (PA1) after NCC migration. This increased cell death can be rescued in utero by pharmacological inhibition of p53. Furthermore, we show that epithelial SHH is necessary for the early differentiation of mandibular cartilage condensations and, therefore, the subsequent development of Meckel's cartilage, around which the dentary bone forms. Nonetheless, a rescue of the cell death phenotype does not rescue the defect in cartilage condensation formation.
  
  
  CONCLUSIONS
  Our results show that SHH produced by the PA1 epithelium is necessary for the survival of post-migratory NCC, and suggests a key role in the subsequent differentiation of chondrocytes to form Meckel's cartilage.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Katherine Kretovich
authors.initials: KK
authors.lastname: Billmyre
authors.forename: John
authors.initials: J
authors.lastname: Klingensmith
mesh_terms: D000818:Animals; D017209:Apoptosis; D001934:Branchial Region / Q000196:embryology* / Q000378:metabolism; D002356:Cartilage / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis; D004475:Ectoderm / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008844:Micrognathism / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D010614:Pharynx / Q000196:embryology; D010641:Phenotype; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C088334:Distal-less homeobox proteins; C501120:Dlx5 protein, mouse; C496457:Fgf8 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C465570:Shh protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051524:Fibroblast Growth Factor 8
keywords: chondrogenesis; micrognathia; neural crest cells