Nakatomi M, Morita I, Eto K, Ota M S
Section of Molecular Craniofacial Embryology, Tokyo Medical and Dental University, Japan.
J Dent Res. 2006 May;85(5):427-31. doi: 10.1177/154405910608500506.
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.
赫特维希上皮根鞘（HERS）对牙根形成很重要，但牙根发育信号传导的分子基础仍不确定。我们推测音猬因子（Shh）信号传导参与HERS功能，因为它在胚胎期牙发生过程中介导上皮-间充质相互作用。我们研究了Shh信号传导在小鼠正在发育的磨牙根中的基因表达模式。在HERS中鉴定出了Shh和Patched2转录本，而Patched1、Smoothened和Gli1除了在HERS中表达外，还在增殖性牙间充质中表达。为了证实Shh信号传导在体内是否具有生理功能，我们分析了携带异常PATCHED1蛋白C末端的间充质发育异常（mes）小鼠。在突变体中，1周时HERS周围的细胞增殖受到抑制。此外，磨牙萌出受到干扰，4周时所有牙根均比对照同窝仔鼠的牙根短。这些结果表明Shh信号传导在牙根发育中很重要。使用的缩写：BrdU，5-溴-2'-脱氧尿苷；HERS，赫特维希上皮根鞘；NFI-C/CTF，核因子Ic/CAAT盒转录因子；PCNA，增殖细胞核抗原；Ptc，patched；Shh，音猬因子；Smo，smoothened。
