Regulation of proliferation in developing human tooth germs by MSX homeodomain proteins and cyclin-dependent kinase inhibitor p19INK4d.

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Organogenesis Pub Date : 2017-10-02 Epub Date: 2017-09-21 DOI:10.1080/15476278.2017.1358337
Darko Kero, Katarina Vukojevic, Petra Stazic, Danijela Sundov, Snjezana Mardesic Brakus, Mirna Saraga-Babic
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引用次数: 14

Abstract

Before the secretion of hard dental tissues, tooth germs undergo several distinctive stages of development (dental lamina, bud, cap and bell). Every stage is characterized by specific proliferation patterns, which is regulated by various morphogens, growth factors and homeodomain proteins. The role of MSX homeodomain proteins in odontogenesis is rather complex. Expression domains of genes encoding for murine Msx1/2 during development are observed in tissues containing highly proliferative progenitor cells. Arrest of tooth development in Msx knockout mice can be attributed to impaired proliferation of progenitor cells. In Msx1 knockout mice, these progenitor cells start to differentiate prematurely as they strongly express cyclin-dependent kinase inhibitor p19INK4d. p19INK4d induces terminal differentiation of cells by blocking the cell cycle in mitogen-responsive G1 phase. Direct suppression of p19INK4d by Msx1 protein is, therefore, important for maintaining proliferation of progenitor cells at levels required for the normal progression of tooth development. In this study, we examined the expression patterns of MSX1, MSX2 and p19INK4d in human incisor tooth germs during the bud, cap and early bell stages of development. The distribution of expression domains of p19INK4d throughout the investigated period indicates that p19INK4d plays active role during human tooth development. Furthermore, comparison of expression domains of p19INK4d with those of MSX1, MSX2 and proliferation markers Ki67, Cyclin A2 and pRb, indicates that MSX-mediated regulation of proliferation in human tooth germs might not be executed by the mechanism similar to one described in developing tooth germs of wild-type mouse.

Abstract Image

Abstract Image

MSX同源结构域蛋白和周期蛋白依赖性激酶抑制剂p19INK4d对人牙胚增殖的调控
在牙齿硬组织分泌出来之前,牙齿细菌经历了几个不同的发育阶段(牙板、牙芽、牙帽和牙钟)。每个阶段都有特定的增殖模式,受各种形态因子、生长因子和同源结构域蛋白的调控。MSX同源结构域蛋白在牙形成中的作用相当复杂。在含有高增殖祖细胞的组织中观察到小鼠发育过程中编码Msx1/2的基因表达域。Msx基因敲除小鼠的牙齿发育受阻可归因于祖细胞增殖受损。在Msx1基因敲除小鼠中,这些祖细胞开始过早分化,因为它们强烈表达周期蛋白依赖性激酶抑制剂p19INK4d。p19INK4d通过阻断有丝分裂原应答G1期的细胞周期诱导细胞终末分化。因此,Msx1蛋白对p19INK4d的直接抑制对于维持牙齿发育正常进程所需的祖细胞增殖水平是重要的。在这项研究中,我们检测了MSX1、MSX2和p19INK4d在人门牙芽、牙盖和钟形发育早期的表达模式。p19INK4d在整个研究期间的表达域分布表明p19INK4d在人类牙齿发育过程中发挥积极作用。此外,p19INK4d的表达域与MSX1、MSX2以及增殖标志物Ki67、Cyclin A2和pRb的表达域比较表明,msx介导的人牙胚增殖调节可能与野生型小鼠牙胚发育中的机制不同。
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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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