A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
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DOI：
10.1038/s41588-018-0080-5
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发表时间：
2018-04-01
期刊：
影响因子：
30.8
通讯作者：
Luis Gomez-Skarmeta, Jose
中科院分区：
文献类型：
--
作者：
Letelier, Joaquin;de la Calle-Mustienes, Elisa;Luis Gomez-Skarmeta, Jose
尽管它们在进化、发育和功能上都很重要，但脊椎动物配对附肢的起源仍然不确定。在小鼠中，称为 ZRS 的单个增强子单独负责四肢中的 Shh 表达。在这里，斑马鱼和小鼠转基因测定追踪了 ZRS 在颚口动物系统发育中的功能等价性。 CRISPR/Cas9 介导的青鳉 (Oryzias latipes) ZRS 删除和增强子检测鉴定了硬骨鱼和人类基因组中 ZRS 影子增强子的存在。 ZRS 和影子 ZRS 的缺失会消除 shh 表达并完全截断胸鳍的形成。引人注目的是，ZRS 的缺失导致背鳍几乎完全消融。这一发现表明，成对鳍和中鳍共享 ZRS-Shh 调节模块，并且成对鳍可能是通过在茎颌类中鳍中建立的发育程序的共同选择而出现的。后来，通过影子增强子的募集，“嘘”功能在胸鳍发育过程中得到了增强，从而赋予了额外的鲁棒性。
Despite their evolutionary, developmental and functional importance, the origin of vertebrate paired appendages remains uncertain. In mice, a single enhancer termed ZRS is solely responsible for Shh expression in limbs. Here, zebrafish and mouse transgenic assays trace the functional equivalence of ZRS across the gnathostome phylogeny. CRISPR/Cas9-mediated deletion of the medaka (Oryzias latipes) ZRS and enhancer assays identify the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolishes shh expression and completely truncates pectoral fin formation. Strikingly, deletion of ZRS results in an almost complete ablation of the dorsal fin. This finding indicates that a ZRS-Shh regulatory module is shared by paired and median fins and that paired fins likely emerged by the co-option of developmental programs established in the median fins of stem gnathostomes. Shh function was later reinforced in pectoral fin development with the recruitment of shadow enhancers, conferring additional robustness.