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TGF-beta signaling and its functional significance in regulating the fate of cranial neural crest cells.转化生长因子-β信号传导及其在调控颅神经嵴细胞命运中的功能意义。
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牙齿发育早期阶段TGFβ/SMAD2信号通路及CCN2/CTGF表达的动态分析

Dynamic analysis of the expression of the TGFbeta/SMAD2 pathway and CCN2/CTGF during early steps of tooth development.

作者信息

Pacheco Marcos S, Reis Alice H, Aguiar Diego P, Lyons Karen M, Abreu José G

机构信息

Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Cells Tissues Organs. 2008;187(3):199-210. doi: 10.1159/000112640. Epub 2007 Dec 17.

DOI:10.1159/000112640
PMID:18089935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2760595/
Abstract

BACKGROUND/AIMS: CCN2 is present during tooth development. However, the relationship between CCN2 and the transforming growth factor beta (TGFbeta)/SMAD2/3 signaling cascade during early stages of tooth development is unclear. Here, we compare the expression of CCN2 and TGFbeta/SMAD2/3 components during tooth development, and analyze the functioning of TGFbeta/SMAD2/3 in wild-type (WT) and Ccn2 null (Ccn2-/-) mice.

METHODS

Coronal sections of mice on embryonic day (E)11.5, E12.5, E13.5, E14.5 and E18.5 from WT and Ccn2-/- were immunoreacted to detect CCN2 and components of the TGFbeta signaling pathway and assayed for 5'-bromo-2'-deoxyuridine immunolabeling and proliferating cell nuclear antigen immunostaining.

RESULTS

CCN2 and TGFbeta signaling components such as TGFbeta1, TGFbeta receptor II, SMADs2/3 and SMAD4 were expressed in inducer tissues during early stages of tooth development. Proliferation analysis in these areas showed that epithelial cells proliferate less than mesenchymal cells from E11.5 to E13.5, while at E14.5 they proliferate more than mesenchymal cells. We did not find a correlation between functioning of the TGFbeta1 cascade and CCN2 expression because Ccn2-/- mice showed neither a reduction in SMAD2 phosphorylation nor a difference in cell proliferation.

CONCLUSION

CCN2 and the TGFbeta/SMAD2/3 signaling pathway are active in signaling centers of tooth development where proliferation is dynamic, but these mechanisms may act independently.

摘要

背景/目的：CCN2在牙齿发育过程中存在。然而，在牙齿发育早期阶段，CCN2与转化生长因子β（TGFβ）/SMAD2/3信号级联之间的关系尚不清楚。在此，我们比较牙齿发育过程中CCN2和TGFβ/SMAD2/3成分的表达，并分析TGFβ/SMAD2/3在野生型（WT）和Ccn2基因敲除（Ccn2-/-）小鼠中的功能。

方法

对野生型和Ccn2-/-小鼠胚胎第（E）11.5天、E12.5天、E13.5天、E14.5天和E18.5天的冠状切片进行免疫反应，以检测CCN2和TGFβ信号通路的成分，并进行5'-溴-2'-脱氧尿苷免疫标记和增殖细胞核抗原免疫染色分析。

结果

CCN2和TGFβ信号成分，如TGFβ1、TGFβ受体II、SMADs2/3和SMAD4在牙齿发育早期的诱导组织中表达。这些区域的增殖分析表明，从E11.5到E13.5，上皮细胞的增殖少于间充质细胞，而在E14.5时，上皮细胞的增殖多于间充质细胞。我们未发现TGFβ1级联功能与CCN2表达之间的相关性，因为Ccn2-/-小鼠既未出现SMAD2磷酸化减少，也未出现细胞增殖差异。

结论

CCN2和TGFβ/SMAD2/3信号通路在牙齿发育的信号中心活跃，在这些中心增殖是动态的，但这些机制可能独立发挥作用。