Wnt Production in Dental Epithelium Is Crucial for Tooth Differentiation
Wnt Production in Dental Epithelium Is Crucial for Tooth Differentiation
复制标题
牙上皮中 Wnt 的产生对于牙齿分化至关重要
DOI：
10.1177/0022034519835194
复制
发表时间：
2019-05-01
影响因子：
7.6
通讯作者：
Zhang, Z.
中科院分区：
文献类型：
--
作者：
Xiong, Y.;Fang, Y.;Zhang, Z.
Wnt配体在发育中的牙齿上表现出各种时空表达。到目前为止，这些差异表达的Wnt配体对牙齿发育的作用尚不清楚。 SHH表达指定在开始期间的牙源性上皮，并且在牙齿发育过程中始终仅限于牙齿上皮。在这项研究中，SHH-CRE通过SHH-CRE的关键调节剂Wntless（WLS）灭活了Wntless（WLS），以研究如何在牙齿发育中如何在牙科上皮谱系中产生的Wnt配体如何产生。我们发现SHH-CRE将WLS的条件敲除导致有缺陷的成成木和Odontoblast分化。 WLS（SHH-CRE）牙齿在底贝阶段表现出内搪瓷上皮和下面的间质的规范Wnt信号传导活性，如靶基因表达和蝙蝠 - 伴形染色所示。 Wnt5a和Wnt10b的表达不会在WLS（SHH-CRE）牙齿中改变。相比之下，Wnt10a的表达显着增加，响应上皮WLS缺乏症。此外，WLS（SHH-CRE）牙齿的刺猬信号通路途径SHH，GLI1和Patched1的表达大大降低。 SHH谱系中的上皮WLS功能丧失还会导致牙齿上皮和间质的异常细胞增殖，在胚胎天第16.5天。但是，细胞凋亡不受影响。此外，我们发现DecorIn和Col1a1（在WLS（SHH-CRE）牙齿中被下调的Odontoblast分化的关键标记物充当染色质免疫注定分析的直接下游靶标的直接下游靶标。此外，在体外牙齿外植体中，可以通过氯化锂（LICL）处理来增加Decorin和col1a1的表达。综上所述，我们的结果表明，牙齿上皮谱系中Wnt配体的空间表达可调节后期牙齿结构的分化。
The Wnt ligands display varied spatiotemporal expression in the epithelium and mesenchyme in the developing tooth. Thus far, the actions of these differentially expressed Wnt ligands on tooth development are not clear. Shh expression specifies the odontogenic epithelium during initiation and is consistently restricted to the dental epithelium during tooth development. In this study, we inactivate Wntless (Wls), the key regulator for Wnt trafficking, by Shh-Cre to investigate how the Wnt ligands produced in the dental epithelium lineage act on tooth development. We find that conditional knockout of Wls by Shh-Cre leads to defective ameloblast and odontoblast differentiation. WlsShh-Cre teeth display reduced canonical Wnt signaling activity in the inner enamel epithelium and the underlying mesenchyme at the early bell stage, as exhibited by target gene expression and BAT-gal staining. The expression of Wnt5a and Wnt10b is not changed in WlsShh-Cre teeth. By contrast, Wnt10a expression is significantly increased in response to epithelial Wls deficiency. In addition, the expression of Hedgehog signaling pathway components Shh, Gli1, and Patched1 was greatly decreased in WlsShh-Cre teeth. Epithelial Wls loss of function in Shh lineage also leads to aberrant cell proliferation in dental epithelium and mesenchyme at embryonic day 16.5; however, the cell apoptosis is unaffected. Moreover, we find that Decorin and Col1a1, the key markers for odontoblast differentiation that are downregulated in WlsShh-Cre teeth, act as direct downstream targets of the canonical Wnt signaling pathway by chromatin immunoprecipitation analysis. Additionally, Decorin and Col1a1 expression can be increased by lithium chloride (LiCl) treatment in the in vitro tooth explants. Taken together, our results suggest that the spatial expression of Wnt ligands within the dental epithelial lineage regulates the differentiation of tooth structures in later stages.