Cilia are present on most vertebrate cells and play a central role in development, growth, and homeostasis. Thus, cilia dysfunction can manifest into an array of diseases, collectively termed ciliopathies, affecting millions of lives worldwide. Yet, our understanding of the gene regulatory networks that control cilia assembly and functions remain incomplete. With the advances in next‐generation sequencing technologies, we can now rapidly predict pathogenic variants from hundreds of ciliopathy patients. While the pace of candidate gene discovery is exciting, most of these genes have never been previously implicated in cilia assembly or function. This makes assigning the disease causality difficult. This review discusses how Xenopus, a genetically tractable and high‐throughput vertebrate model, has played a central role in identifying, validating, and characterizing candidate ciliopathy genes. The review is focused on multiciliated cells (MCCs) and diseases associated with MCC dysfunction. MCCs harbor multiple motile cilia on their apical surface to generate extracellular fluid flow inside the airway, the brain ventricles, and the oviduct. In Xenopus, these cells are external and present on the embryonic epidermal epithelia, facilitating candidate genes analysis in MCC development in vivo. The ability to introduce patient variants to study their effects on disease progression makes Xenopus a powerful model to improve our understanding of the underlying disease mechanisms and explain the patient phenotype.

中文翻译：

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拯救非洲爪蟾：验证和表征候选纤毛病基因的模型

纤毛存在于大多数脊椎动物细胞中，在发育、生长和体内平衡中发挥核心作用。因此，纤毛功能障碍可以表现为一系列疾病，统称为纤毛病，影响全世界数百万人的生命。然而，我们对控制纤毛组装和功能的基因调控网络的理解仍然不完整。随着新一代测序技术的进步，我们现在可以快速预测数百名纤毛病患者的致病变异。虽然候选基因发现的步伐令人兴奋，但这些基因中的大多数以前从未涉及纤毛组装或功能。这使得分配疾病因果关系变得困难。这篇评论讨论了非洲爪蟾如何是一种遗传易处理且高通量的脊椎动物模型，在识别、验证和表征候选纤毛病基因方面发挥了核心作用。该评论的重点是多纤毛细胞 (MCC) 和与 MCC 功能障碍相关的疾病。MCC 在其顶端表面具有多个运动纤毛，以在气道、脑室和输卵管内产生细胞外液流。在非洲爪蟾中，这些细胞在体外并存在于胚胎表皮上皮细胞上，促进体内MCC 发育的候选基因分析。引入患者变异以研究它们对疾病进展的影响的能力使非洲爪蟾 一个强大的模型，可以提高我们对潜在疾病机制的理解并解释患者的表型。