Evolution of the endothelin pathway drove neural crest cell diversification
Evolution of the endothelin pathway drove neural crest cell diversification
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DOI：
10.1038/s41586-020-2720-z
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发表时间：
2020-09-16
期刊：
影响因子：
64.8
通讯作者：
Medeiros, Daniel M.
中科院分区：
文献类型：
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作者：
Square, Tyler A.;Jandzik, David;Medeiros, Daniel M.
CRISPR-Cas9介导的海七鳃鳗Petromyzon marinus和蛙Xenopus laevis中内皮素信号传导途径的破坏被用于描绘内皮素信号传导的古老和谱系特异性作用，并提供对脊椎动物进化的见解。神经嵴细胞（NCC）是脊椎动物特有的迁移性多能胚胎细胞，形成一系列分支定义的成年特征。NCC的进化与各种基因组事件有关，包括新基因调控网络的进化（1，2），基因的从头进化（3）和全基因组复制事件期间旁系同源基因的增殖（4）。然而，缺乏将新的和/或重复的基因与NCC进化联系起来的决定性功能证据。内皮素配体（Edns）和内皮素受体（Ednrs）是脊椎动物所特有的（3，5，6），并且调节有颌脊椎动物中NCC发育的多个方面（7-10）。在这里，为了测试Edn信号传导的进化是否是NCC进化的驱动因素，我们使用CRISPR-Cas9诱变（11）来破坏海七鳃鳗Petromyzon marinus中的Edn，ednrandlxgenes。七鳃鳗是一种无颌鱼类，大约在5亿年前与现代有颌脊椎动物共享一个共同的祖先（12）。因此，七鳃鳗和有颌类之间的比较可以确定脊椎动物发育的高度保守和进化灵活的特征。使用frogXenopus laevisto扩大gnathostome系统发育的代表性，并促进并排分析，我们确定古老的和特定谱系的作用Edn信号。这些发现表明，Edn信号在脊椎动物基因组复制之前在NCC中被激活。然后，在脊椎动物干细胞中的一个或多个全基因组复制后，旁系同源Edn通路在功能上发生分歧，导致具有不同Edn信号传导要求的NCC亚群。我们认为这种新的发育模块性促进了NCC衍生物在干脊椎动物中的独立进化。与此相一致，Edn通路靶点的差异与七鳃鳗和现代颌口鱼的口咽骨骼和自主神经系统的差异有关。总之，我们的工作提供了功能遗传学证据，将新脊椎动物基因的起源和复制与定义脊椎新奇的逐步进化联系起来。
CRISPR-Cas9-mediated disruption of the endothelin-signalling pathway in the sea lampreyPetromyzon marinusand the frogXenopus laeviswere used to delineate ancient and lineage-specific roles of endothelin signalling and provide insights into vertebrate evolution.Neural crest cells (NCCs) are migratory, multipotent embryonic cells that are unique to vertebrates and form an array of clade-defining adult features. The evolution of NCCs has been linked to various genomic events, including the evolution of new gene-regulatory networks(1,2), the de novo evolution of genes(3)and the proliferation of paralogous genes during genome-wide duplication events(4). However, conclusive functional evidence linking new and/or duplicated genes to NCC evolution is lacking. Endothelin ligands (Edns) and endothelin receptors (Ednrs) are unique to vertebrates(3,5,6), and regulate multiple aspects of NCC development in jawed vertebrates(7-10). Here, to test whether the evolution of Edn signalling was a driver of NCC evolution, we used CRISPR-Cas9 mutagenesis(11)to disruptedn,ednranddlxgenes in the sea lamprey,Petromyzon marinus. Lampreys are jawless fishes that last shared a common ancestor with modern jawed vertebrates around 500 million years ago(12). Thus, comparisons between lampreys and gnathostomes can identify deeply conserved and evolutionarily flexible features of vertebrate development. Using the frogXenopus laevisto expand gnathostome phylogenetic representation and facilitate side-by-side analyses, we identify ancient and lineage-specific roles for Edn signalling. These findings suggest that Edn signalling was activated in NCCs before duplication of the vertebrate genome. Then, after one or more genome-wide duplications in the vertebrate stem, paralogous Edn pathways functionally diverged, resulting in NCC subpopulations with different Edn signalling requirements. We posit that this new developmental modularity facilitated the independent evolution of NCC derivatives in stem vertebrates. Consistent with this, differences in Edn pathway targets are associated with differences in the oropharyngeal skeleton and autonomic nervous system of lampreys and modern gnathostomes. In summary, our work provides functional genetic evidence linking the origin and duplication of new vertebrate genes with the stepwise evolution of a defining vertebrate novelty.