Wnt10a-Notch信号轴控制着赫氏上皮根鞘细胞在根皮毛形成过程中的行为。

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Kai Sun, Miao Yu, Jiayu Wang, Hu Zhao, Haochen Liu, Hailan Feng, Yang Liu, Dong Han
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引用次数: 0

摘要

WNT10A双等位突变的人类和上皮Wnt10a基因敲除的小鼠表现出牙髓腔扩大和多生根牙齿根嵴顶端移位,即所谓的 "陶牙症",从而表明Wnt10a在牙根形态发生中的关键作用。然而,上皮Wnt10a调控赫氏上皮根鞘(HERS)细胞行为并促进牙根沟形态形成的内源机制仍不清楚。在这项研究中,我们发现从出生后第 0.5 天(PN0.5)到出生后第 4.5 天,K14-Cre;Wnt10afl/fl 小鼠推定根皮毛区的 HERS 未能以适当的水平伸长。EdU测定和细胞周期蛋白D1免疫荧光染色显示,K14-Cre;Wnt10afl/fl小鼠HERS内釉上皮(IEE)细胞的增殖活性在PN2.5和PN3.5时明显下降。E-Cadherin和乙酰基-α-微管蛋白的免疫荧光染色表明,HERS的IEE细胞倾向于垂直于水平面分裂,这阻碍了HERS在K14-Cre;Wnt10afl/fl小鼠的假定根皮脂区的水平延伸。RNA-seq和免疫荧光显示,K14-Cre;Wnt10afl/fl小鼠HERS的IEE细胞中Jag1和Notch2的表达下调。此外,通过Notch2腺病毒和肾囊移植激活K14-Cre;Wnt10afl/fl小鼠磨牙中的Notch信号后,牙根沟缺陷得到了部分修复。综上所述,我们的研究表明,上皮 Wnt10a-Notch 信号轴在牙根犁沟形态发生过程中对于调节 HERS 细胞的正常增殖和水平定向分裂至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.

A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/fl mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10afl/fl mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/fl mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10afl/fl molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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