title: Hedgehog signaling regulates dental papilla formation and tooth size during zebrafish odontogenesis.
abstract: BACKGROUND
  Intercellular communication by the hedgehog cell signaling pathway is necessary for tooth development throughout the vertebrates, but it remains unclear which specific developmental signals control cell behavior at different stages of odontogenesis. To address this issue, we have manipulated hedgehog activity during zebrafish tooth development and visualized the results using confocal microscopy.
  
  
  RESULTS
  We first established that reporter lines for dlx2b, fli1, NF-κB, and prdm1a are markers for specific subsets of tooth germ tissues. We then blocked hedgehog signaling with cyclopamine and observed a reduction or elimination of the cranial neural crest derived dental papilla, which normally contains the cells that later give rise to dentin-producing odontoblasts. Upon further investigation, we observed that the dental papilla begins to form and then regresses in the absence of hedgehog signaling, through a mechanism unrelated to cell proliferation or apoptosis. We also found evidence of an isometric reduction in tooth size that correlates with the time of earliest hedgehog inhibition.
  
  
  CONCLUSIONS
  We hypothesize that these results reveal a previously uncharacterized function of hedgehog signaling during tooth morphogenesis, regulating the number of cells in the dental papilla and thereby controlling tooth size.
authors: Biology Department, Bowdoin College, Brunswick, Maine.
authors: Jeffrey C
authors: JC
authors: Yu
authors: Zachary D
authors: ZD
authors: Fox
authors: James L
authors: JL
authors: Crimp
authors: Hana E
authors: HE
authors: Littleford
authors: Andrea L
authors: AL
authors: Jowdry
authors: William R
authors: WR
authors: Jackman
mesh_terms: D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D003771:Dental Papilla / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009024:Morphogenesis; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009804:Odontoblasts / Q000378:metabolism*; D009805:Odontogenesis / Q000502:physiology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D015398:Signal Transduction; D014070:Tooth / Q000196:embryology*; D014083:Tooth Germ / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000737:chemistry; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C088334:Distal-less homeobox proteins; C000598206:Fli1b protein, zebrafish; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; C513257:prdm1a protein, zebrafish; C000541:cyclopamine
keywords: cell signaling; cyclopamine; morphogenesis; odontoblasts; teeth
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