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New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox

机译:照亮甲状腺器官发生的新模型系统。第一部分:Zebrafish工具箱的更新

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摘要

Thyroid dysgenesis (TD) resulting from defects during embryonic thyroid development represents a major cause of congenital hypothyroidism. The pathogenetic mechanisms of TD in human newborns, however, are still poorly understood and disease-causing genetic variants have been identified in only a small percentage of TD cases. This limited understanding of the pathogenesis of TD is partly due to a lack of knowledge on how intrinsic factors and extrinsic signalling cues orchestrate the differentiation of thyroid follicular cells and the morphogenesis of thyroid tissue. Recently, embryonic stem cells and zebrafish embryos emerged as novel model systems that allow for innovative experimental approaches in order to decipher cellular and molecular mechanisms of thyroid development and to unravel pathogenic mechanisms of TD. Zebrafish embryos offer several salient properties for studies on thyroid organogenesis including rapid and external development, optical transparency, ease of breeding, relative short generation time and amenability for genome editing. In this review, we will highlight recent advances in the zebrafish toolkit to visualize cellular dynamics of organ development and discuss specific prospects of the zebrafish model for studies on vertebrate thyroid development and human congenital thyroid diseases.
机译:由胚胎甲状腺发育过程中的缺陷引起的甲状腺发育不良(TD)是先天性甲状腺功能低下的主要原因。然而,TD在人类新生儿中的致病机理仍然知之甚少,并且仅在很小比例的TD病例中就已经确定了致病的遗传变异。对TD发病机理的有限了解部分是由于缺乏对内在因素和外在信号提示如何协调甲状腺滤泡细胞分化和甲状腺组织形态发生的认识。最近,胚胎干细胞和斑马鱼胚胎以新颖的模型系统出现,它们允许采用创新的实验方法来破译甲状腺发育的细胞和分子机制,并阐明TD的致病机制。斑马鱼胚胎为甲状腺器官发生的研究提供了几个显着特性,包括快速和外部发育,光学透明性,易于繁殖,相对较短的生成时间以及基因组编辑的便利性。在这篇综述中,我们将重点介绍斑马鱼工具箱中的最新进展,以可视化器官发育的细胞动力学,并讨论斑马鱼模型在脊椎动物甲状腺发育和人类先天性甲状腺疾病研究中的特定前景。

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