Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development.
Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development.
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DOI：
10.1016/j.archoralbio.2009.09.005
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发表时间：
2009-12
影响因子：
3
通讯作者：
Brook, A. H.
中科院分区：
文献类型：
--
作者：
Brook, A. H.
牙齿异常是牙齿发育过程中遗传、表观遗传和环境因素相互作用的结果。这一进程是多因素、多层次、多层面的，并随着时间的推移而逐步展开。本文综合了动物模型和人体研究的证据，概述了目前的地位，并构建和评估模型，作为未来工作的基础。牙齿发育是多层次的，需要分子和细胞的相互作用，具有宏观的结果。它是多维的，需要三个空间维度和第四维时间的发展。它是渐进的，发生在一个很长的时期，但有关键的阶段。涉及多个遗传信号通路的一系列相互作用也受到细胞外因子的影响。多个基因的相互作用、梯度效应和空间场效应、表观遗传因素和环境因素都影响单个牙齿、牙齿组和整个牙列的发育。人类的宏观临床可见结果是在形态发生场中形成的四种不同牙齿类型的复杂单元，其中每个场中的牙齿定向形成并在不同时间萌出，反映了发育的时空控制。即使在患有牙齿异常的患者中鉴定出单个基因的特定突变或一种主要的环境损伤，对表型的详细研究也常常揭示出同一家族中受影响的个体之间、同一个体中的牙列之间甚至同一牙列中的不同牙齿之间的变异。相同或非常相似的表型，无论是牙齿数量或结构的异常，可能源于不同的病因：不仅不同基因的突变，而且环境因素也可能导致相似的表型。在不同的组织中，与许多在牙齿发生中活跃的发育调节基因的作用相关，突变可导致牙齿异常是其中一部分的综合征。发育调控基因之间的拮抗平衡被破坏，作为激活剂或抑制剂，可导致牙齿异常。在个别牙胚的发育过程中存在关键阶段，如果进展失败，牙胚将不会进一步发育或经历细胞凋亡。在起始和形态发生的顺序过程中，随时间推移的反复信号模式反映在数量、大小和形式异常与拟议模型的临床相关性中。未来研究的第一步是将联合收割机的遗传学研究与表型的精确记录和测量相结合。他们还需要整理每个水平的发现，并利用现在可能的人类和小鼠表型的准确定义。
Dental anomalies are caused by complex interactions between genetic, epigenetic and environmental factors during the long process of dental development. This process is multifactorial, multilevel, multidimensional and progressive over time. In this paper the evidence from animal models and from human studies is integrated to outline the current position and to construct and evaluate models, as a basis for future work. Dental development is multilevel entailing molecular and cellular interactions which have macroscopic outcomes. It is multidimensional, requiring developments in the three spatial dimensions and the fourth dimension of time. It is progressive, occurring over a long period, yet with critical stages. The series of interactions involving multiple genetic signalling pathways are also influenced by extracellular factors. Interactions, gradients and spatial field effects of multiple genes, epigenetic and environmental factors all influence the development of individual teeth, groups of teeth and the dentition as a whole. The macroscopic, clinically visible result in humans is a complex unit of four different tooth types formed in morphogenetic fields, in which teeth within each field form directionally and erupt at different times, reflecting the spatio-temporal control of development. Even when a specific mutation of a single gene or one major environmental insult has been identified in a patient with a dental anomaly, detailed investigation of the phenotype often reveals variation between affected individuals in the same family, between dentitions in the same individual and even between different teeth in the same dentition. The same, or closely similar phenotypes, whether anomalies of tooth number or structure, may arise from different aetiologies: not only mutations in different genes but also environmental factors may result in similar phenotypes. Related to the action of a number of the developmental regulatory genes active in odontogenesis, in different tissues, mutations can result in syndromes of which dental anomalies are part. Disruption of the antagonistic balance between developmental regulatory genes, acting as activators or inhibitors can result in dental anomalies. There are critical stages in the development of the individual tooth germs and, if progression fails, the germ will not develop further or undergoes apoptosis. The reiterative signalling patterns over time during the sequential process of initiation and morphogenesis are reflected in the clinical association of anomalies of number, size and form and the proposed models. An initial step in future studies is to combine the genetic investigations with accurate recording and measurement of the phenotype. They also need to collate findings at each level and exploit the accurate definition of both human and murine phenotypes now possible.
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DOI：
10.1111/j.1600-0528.1986.tb01493.x
发表时间：
1986-02-01
影响因子：
2.3
作者：
BACKMAN, B;HOLM, AK
通讯作者：
HOLM, AK
影响因子：
7.6
作者：
Bartlett, JD;Beniash, E;Smith, CE
通讯作者：
Smith, CE
影响因子：
3
作者：
Brook, A. H.;Elcock, C.;Smith, R. N.
通讯作者：
Smith, R. N.
影响因子：
2.6
作者：
BROOK, AH;WINTER, GB
通讯作者：
WINTER, GB
影响因子：
3
作者：
Brook, A. H.;Griffin, R. C.;Smith, R. N.
通讯作者：
Smith, R. N.