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Sonic hedgehog regulates morphogenesis, cell proliferation and and differentiation in developing tooth germs.

Sonic Hedgehog 调节发育中的牙胚的形态发生、细胞增殖和分化。

基本信息

批准号：
10470380
负责人：
KURISU Kojiro
金额：
$ 6.53万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470380/
关键词：
tooth germ Sonic hedgehog organ culture mouse morphogenesis development antisense oligo differentiation

项目摘要

Sonic hedgehog (Shh) is expressed in specific spatio-temporal patterns during odontogenesis, but the specific roles played by this signaling effector are not clear. To address this question, molar tooth germs from E11 and E14 mouse embryos were maintained in organ culture conditions, which allow continuation of their development, in the absence or presence of antisense Shh oligonucleotides. RT-PCR and immunohistological analyses showed that a marked and selective reduction of endogenous Shh expression was caused by antisense oligonucleotide treatment, whereas sense, random or mutated antisense oligomers had no effect. Inhibition of Shh expression in cultured E11 lamina stage tooth germs prevented their progression to the cap stage seen in companion control germs and was accompanied by a sharp reduction of proliferation in both epithelial and mesenchymal cells and down-regulation of hedgehog signal-mediating molecules Patched-1, Patched-2 and Gli-1. Likewise, Shh inhibition in E14 germs led not only to a severe growth retardation but also severe abnormalities in morphogenesis and cytodifferentiation. Control E14 cap stage germs advanced to the bell stage and displayed conspicuous cusps, ameloblasts and odontoblasts, whereas the antisense-treated germs lacked both cusps and differentiated cells. These results show that Shh is an essential factor for normal tooth development is appeared to be required for multiple events, including morphogenesis, cell proliferation and cytodifferentiation.

Sonic hedgehog （Shh）在牙形成过程中以特定的时空模式表达，但该信号效应物的具体作用尚不清楚。为了解决这个问题，我们将来自E11和E14小鼠胚胎的臼齿细菌保存在器官培养条件下，在没有或存在反义Shh寡核苷酸的情况下，允许其继续发育。RT-PCR和免疫组织学分析表明，反义寡核苷酸处理可显著和选择性地降低内源性Shh的表达，而正义、随机或突变的反义寡核苷酸则没有作用。在培养的E11牙胚中，抑制Shh的表达阻止了其向帽期的发展，并伴随着上皮细胞和间充质细胞增殖的急剧减少，以及hedgehog信号介导分子patch -1、patch -2和gli1的下调。同样，Shh在E14细菌中的抑制不仅会导致严重的生长迟缓，还会导致严重的形态发生和细胞分化异常。对照E14帽期细菌进入钟形期，出现明显的尖状细胞、成釉细胞和成牙细胞，而反义处理的细菌既没有尖状细胞，也没有分化细胞。这些结果表明Shh是正常牙齿发育的一个重要因子，似乎是包括形态发生、细胞增殖和细胞分化在内的多个事件所必需的。