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Deficiency of zebrafish fgf20a results in aberrant skull remodeling that mimics both human cranial disease and evolutionarily important fish skull morphologies

机译:斑马鱼fgf20a的缺乏会导致颅骨异常重塑从而模仿人类颅脑疾病和具有进化重要性的鱼类颅骨形态

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摘要

The processes that direct skull remodeling are of interest to both human-oriented studies of cranial dysplasia and evolutionary studies of skull divergence. There is increasing awareness that these two fields can be mutually informative when natural variation mimics pathology. Here we describe a zebrafish mutant line, devoid of blastema(dob), which does not have a functional fgf20a protein, and which also presents cranial defects similar to both adaptive and clinical variation. We used geometric morphometric methods to provide quantitative descriptions of the effects of the dob mutation on skull morphogenesis. In combination with whole-mount in situ hybridization labeling of normal fgf20a expression and assays for osteoblast and osteoclast activity, the results of these analyses indicate that cranial dysmorphologies in dob zebrafish are generated by aberrations in post-embryonic skull remodeling via decreased osteoblasotgenesis and increased osteoclastogenesis. Mutational effects include altered skull vault geometries and midfacial hypoplasia that are consistent with key diagnostic signs for multiple human craniofacial syndromes. These phenotypic shifts also mimic changes in the functional morphology of fish skulls that have arisen repeatedly in several highly successful radiations (e.g., damselfishes and East-African rift-lake cichlids). Our results offer the dob/fgf20a mutant as an experimentally tractable model with which to examine post-embryonic skull development as it relates to human disease and evolution.
机译:面向人类的颅骨发育不良研究和颅骨发散的进化研究都对指导颅骨重塑的过程感兴趣。人们越来越意识到,当自然变化模仿病理时,这两个领域可以相互提供信息。在这里,我们描述了没有blastema(dob)的斑马鱼突变株,它不具有功能性fgf20a蛋白,并且还表现出类似于适应性和临床变异的颅骨缺损。我们使用几何形态计量学方法提供了dob突变对颅骨形态发生的影响的定量描述。结合正常fgf20a表达的全量原位杂交标记以及成骨细胞和破骨细胞活性的测定,这些分析的结果表明,多巴斑马鱼的颅骨畸形是由胚后颅骨重塑中的畸变产生的,这些畸变是通过减少成骨细胞和增加破骨细胞产生的。变异影响包括颅骨穹顶几何形状的改变和面中发育不全,与多种人类颅面综合征的关键诊断体征一致。这些表型变化还模仿了鱼头骨的功能形态变化,这些变化在多次成功的辐射(例如,雀鲷和东非裂谷丽鱼科鱼)中反复出现。我们的结果提供了dob / fgf20a突变体作为实验上易处理的模型,可用来检查与人类疾病和进化有关的胚胎后颅骨发育。

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