Sonic hedgehog signaling is important in tooth root development.
Hertwig's epithelial root sheath (HERS) is important for tooth root formation, but the molecular basis for the signaling of root development remains uncertain. We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS function, because it mediates epithelial-mesenchymal interactions during embryonic odontogenesis. We examined the gene expression patterns of Shh signaling in murine developing molar roots. Shh and Patched2 transcripts were identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in the proliferative dental mesenchyme in addition to the HERS. To confirm whether Shh signaling physiologically functions in vivo, we analyzed mesenchymal dysplasia (mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover, the molar eruption was disturbed, and all roots were shorter than those in control littermates at 4 wks. These results indicate that Shh signaling is important in tooth root development. Abbreviations used: BrdU, 5-bromo-2'-deoxyuridine; HERS, Hertwig's epithelial root sheath; NFI-C/CTF, nuclear factor Ic/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc, patched; Shh, sonic hedgehog; Smo, smoothened.
Nakatomi
M
M
Section of Molecular Craniofacial Embryology, Tokyo Medical and Dental University, Japan.
Morita
I
I
Eto
K
K
Ota
M S
MS
D000818:Animals; D049109:Cell Proliferation; D004848:Epithelium; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics; D009805:Odontogenesis / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014078:Tooth Eruption / Q000235:genetics; D014092:Tooth Root / Q000254:growth & development*; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1
C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; C000606240:Ptch1 protein, mouse; C000606241:Ptch2 protein, mouse; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1