Cichlid fishes as a model to understand normal and clinical craniofacial variation.
Cichlid fishes as a model to understand normal and clinical craniofacial variation.
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丽鱼科鱼是一种了解正常和临床颅面变异的模型。
DOI：
10.1016/j.ydbio.2015.12.018
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发表时间：
2016-07-15
影响因子：
2.7
通讯作者：
Albertson RC
中科院分区：
文献类型：
--
作者：
Powder KE;Albertson RC
我们在理解颅面疾病的病因学方面取得了很大的进步，特别是对于“简单”的孟德尔特征。然而，面部骨骼是一个复杂的特征，影响其最终几何形状的所有遗传、发育和环境因素仍未得到解决。由于通常鉴定的基因和等位基因的类型、发育多效性以及关于环境相互作用的影响的有限信息，正向遗传筛选在复杂性状方面受到限制。在这里，我们讨论了进化模型--非洲慈鲷鱼--的研究如何补充传统方法，以了解复杂形状的遗传和发育起源。慈鲷表现出无与伦比的自然颅面形态，模拟正常人类的变化，并在某些情况下模仿人类面部畸形。此外，慈鲷科鱼类的进化历史和基因组结构使它们成为通过数量性状基因座（QTL）定位和群体基因组学鉴定这些表型的遗传基础的理想系统。鉴于发育基因和途径的分子保守性，慈鲷的见解适用于人类面部变异和疾病。我们回顾了最近的工作，在这个系统中，已确定lbh作为一种新的调节神经嵴细胞迁移，确定Wnt和刺猬途径介导的物种特异性骨形态，并研究如何塑料反应饮食调节成人面部形状。这些研究不仅揭示了现有途径在颅面发育中的新作用，而且确定了参与颅面骨骼形成的新基因和机制。总之，我们认为，结合传统的实验室和进化模型的工作提供了巨大的潜力，提供了一个更完整和全面的图片的无数因素，参与发展的复杂性状。
We have made great strides towards understanding the etiology of craniofacial disorders, especially for ‘simple’ Mendelian traits. However, the facial skeleton is a complex trait, and the full spectrum of genetic, developmental, and environmental factors that contribute to its final geometry remain unresolved. Forward genetic screens are constrained with respect to complex traits due to the types of genes and alleles commonly identified, developmental pleiotropy, and limited information about the impact of environmental interactions. Here, we discuss how studies in an evolutionary model – African cichlid fishes – can complement traditional approaches to understand the genetic and developmental origins of complex shape. Cichlids exhibit an unparalleled range of natural craniofacial morphologies that model normal human variation, and in certain instance mimic human facial dysmorphologies. Moreover, the evolutionary history and genomic architecture of cichlids make them an ideal system to identify the genetic basis of these phenotypes via quantitative trait loci (QTL) mapping and population genomics. Given the molecular conservation of developmental genes and pathways, insights from cichlids are applicable to human facial variation and disease. We review recent work in this system, which has identified lbh as a novel regulator of neural crest cell migration, determined the Wnt and Hedgehog pathways mediate species-specific bone morphologies, and examined how plastic responses to diet modulate adult facial shapes. These studies have not only revealed new roles for existing pathways in craniofacial development, but have identified new genes and mechanisms involved in shaping the craniofacial skeleton. In all, we suggest that combining work in traditional laboratory and evolutionary models offers significant potential to provide a more complete and comprehensive picture of the myriad factors that are involved in the development of complex traits.