Nakamura Tetsuya, Gehrke Andrew R, Lemberg Justin, Szymaszek Julie, Shubin Neil H
Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
Nature. 2016 Sep 8;537(7619):225-228. doi: 10.1038/nature19322. Epub 2016 Aug 17.
Understanding the evolutionary transformation of fish fins into tetrapod limbs is a fundamental problem in biology. The search for antecedents of tetrapod digits in fish has remained controversial because the distal skeletons of limbs and fins differ structurally, developmentally, and histologically. Moreover, comparisons of fins with limbs have been limited by a relative paucity of data on the cellular and molecular processes underlying the development of the fin skeleton. Here, we provide a functional analysis, using CRISPR/Cas9 and fate mapping, of 5' hox genes and enhancers in zebrafish that are indispensable for the development of the wrists and digits of tetrapods. We show that cells marked by the activity of an autopodial hoxa13 enhancer exclusively form elements of the fin fold, including the osteoblasts of the dermal rays. In hox13 knockout fish, we find that a marked reduction and loss of fin rays is associated with an increased number of endochondral distal radials. These discoveries reveal a cellular and genetic connection between the fin rays of fish and the digits of tetrapods and suggest that digits originated via the transition of distal cellular fates.
理解鱼类鳍向四足动物肢体的进化转变是生物学中的一个基本问题。在鱼类中寻找四足动物指(趾)的前身一直存在争议,因为肢体和鳍的远端骨骼在结构、发育和组织学上存在差异。此外,鳍与肢体的比较受到鳍骨骼发育潜在细胞和分子过程数据相对匮乏的限制。在这里,我们利用CRISPR/Cas9和命运图谱对斑马鱼中对四足动物腕部和指(趾)发育不可或缺的5'hox基因和增强子进行了功能分析。我们发现,由一个 autopodial hoxa13增强子的活性标记的细胞专门形成鳍褶的元素,包括真皮鳍条的成骨细胞。在hox13基因敲除的鱼类中,我们发现鳍条的显著减少和缺失与软骨内远端桡骨数量的增加有关。这些发现揭示了鱼类鳍条与四足动物指(趾)之间的细胞和遗传联系,并表明指(趾)起源于远端细胞命运的转变。