The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

译文

Dlx同源盒基因家族以复杂的模式在胚胎颅面外胚层和外间质内表达。先前的研究表明,Dlx-2对于鼠的第一和第二分支弓近端区域的发育至关重要。在这里,我们描述了具有Dlx-1和Dlx-1和-2突变的小鼠的颅面表型。具有Dlx-1和Dlx-1和-2突变的小鼠的骨骼和软组织分析提供了其他证据,证明Dlx基因调节the弓的近现代模式。该分析还阐明了Dlx-1和Dlx-2在颅面发育中的独特作用和重叠作用。此外,缺乏Dlx-1和-2的小鼠具有独特的异常,包括不存在上颌磨牙。 Dlx-1和-2在近端和远端第一和第二弓形中表达,但仅近端区域异常。 Dlx-1,-2,-3,-5和-6的嵌套表达模式为预测每个基因的区域特定要求的模型提供了证据。最后,Dlx-2,Dlx-1和-2突变体具有异位的头骨成分,类似于在系统发育较原始的脊椎动物中发现的骨骼和软骨。

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