Opitz Robert, Antonica Francesco, Costagliola Sabine
Institute of Interdisciplinary Research in Molecular Human Biology, Université Libre de Bruxelles, Brussels, Belgium.
Eur Thyroid J. 2013 Dec;2(4):229-42. doi: 10.1159/000357079. Epub 2013 Dec 3.
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.
胚胎甲状腺发育过程中的缺陷导致的甲状腺发育不全(TD)是先天性甲状腺功能减退症的主要原因。然而,人类新生儿TD的发病机制仍知之甚少,仅在一小部分TD病例中发现了致病基因变异。对TD发病机制的这种有限理解部分是由于缺乏关于内在因素和外在信号线索如何协调甲状腺滤泡细胞分化和甲状腺组织形态发生的知识。最近,胚胎干细胞和斑马鱼胚胎成为新型模型系统,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,并揭示TD的致病机制。斑马鱼胚胎为甲状腺器官发生研究提供了几个显著特性,包括快速的外部发育、光学透明性、易于繁殖、相对较短的世代时间以及适合基因组编辑。在这篇综述中,我们将重点介绍斑马鱼工具包在可视化器官发育细胞动态方面的最新进展,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具体前景。