美国科罗拉多大学Daniel M. Medeiros、David Jandzik以及Tyler A. Square研究组合作取得最新进展。他们发现内皮素的进化途径促使神经嵴细胞的多样化。该项研究成果发表在2020年9月16日出版的《自然》杂志上。
为了研究内皮素配体（Edns）信号的进化是否是NCC进化的驱动力，他们使用CRISPR–Cas9突变了海南鳗（Petromyzon marinus）的Edns、内皮素受体（Ednrs）和dlx基因。海南鳗是无颚鱼类，出现在大约5亿年前，与现代颚脊椎动物有最后的共同祖先。因此，海南鳗和咬足动物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。
使用非洲爪蟾来扩展咬足动物的系统发生学，代表并促进并排分析，他们确定了Edn信号传导的古老的、特定谱系的作用。这些发现表明，在脊椎动物基因组重复之前，Edn信号在NCC中被激活。然后，在脊椎动物茎中进行一个或多个全基因组复制后，旁源Edn途径功能发生分歧，导致具有不同Edn信号传导需求的NCC亚群的形成。
他们认为，这种新的发育模块化，促进了茎脊椎动物中NCC衍生物的独立进化。与此相一致，Edn通路靶点的差异与海南鳗和现代咬足动物的口咽骨骼和自主神经系统的差异有关。总而言之，他们的工作提供了功能遗传证据，将新脊椎动物基因的起源和重复与脊椎动物新事物的逐步进化联系起来。
研究人员表示，NCC是迁移的、多能胚胎细胞，对于脊椎动物而言是独特的，并形成了一系列进化枝定义的成年特征。NCC的进化与各种基因组事件相关，包括新基因调控网络的进化，基因的从头进化和全基因组复制事件期间旁系基因的增殖。但是，缺乏将新的和/或重复的基因与NCC进化联系起来的确凿的功能证据。内皮素配体Edns和内Ednrs是脊椎动物所特有的，并调节有颚脊椎动物中NCC发育的多个方面。
附：英文原文
Title: Evolution of the endothelin pathway drove neural crest cell diversification
Author: Tyler A. Square, David Jandzik, James L. Massey, Marek Romek, Haley P. Stein, Andrew W. Hansen, Amrita Purkayastha, Maria V. Cattell, Daniel M. Medeiros
Issue&Volume: 2020-09-16
Abstract: 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 networks1,2, the de novo evolution of genes3 and the proliferation of paralogous genes during genome-wide duplication events4. 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 vertebrates3,5,6, and regulate multiple aspects of NCC development in jawed vertebrates7,8,9,10. Here, to test whether the evolution of Edn signalling was a driver of NCC evolution, we used CRISPR–Cas9 mutagenesis11 to disrupt edn, ednr and dlx genes in the sea lamprey, Petromyzon marinus. Lampreys are jawless fishes that last shared a common ancestor with modern jawed vertebrates around 500 million years ago12. Thus, comparisons between lampreys and gnathostomes can identify deeply conserved and evolutionarily flexible features of vertebrate development. Using the frog Xenopus laevis to 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.
DOI: 10.1038/s41586-020-2720-z
Source: https://www.nature.com/articles/s41586-020-2720-z
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
