Abstract：
Activin signaling is essential for proper embryonic, skeletal muscle, and reproductive development. Duplication of the pathway in teleost fish has enabled diversification of gene function across the pathway but how gene duplication influences the function of activin signaling in non-mammalian species is poorly understood. Full characterization of activin receptor signaling pathway expression was performed across embryonic development and during early skeletal muscle growth in rainbow trout (RBT, Oncorhynchus mykiss). Rainbow trout are a model salmonid species that have undergone two additional rounds of whole genome duplication. A small number of genes were expressed early in development and most genes increased expression throughout development. There was limited expression of activin Ab in RBT embryos despite these genes exhibiting significantly elevated expression in post-hatch skeletal muscle. CRISPR editing of the activin Aa1 ohnolog and subsequent production of meiotic gynogenetic offspring revealed that biallelic disruption of activin Aa1 did not result in developmental defects, as occurs with knockout of activin A in mammals. The majority of gynogenetic offspring exhibited homozygous activin Aa1 genotypes (wild type, in-frame, or frameshift) derived from the mosaic founder female. The research identifies mechanisms of specialization among the duplicated activin ohnologs across embryonic development and during periods of high muscle growth in larval and juvenile fish. The knowledge gained provides insights into potential viable gene-targeting approaches for engineering the activin receptor signaling pathway and establishes the feasibility of employing meiotic gynogenesis as a tool for producing homozygous F1 genome-edited fish for species with long-generation times, such as salmonids.
摘要：
激活素信号对正常胚胎至关重要，骨骼肌,和生殖发展。该途径在硬骨鱼中的重复使整个途径的基因功能多样化，但是基因重复如何影响非哺乳动物物种中活化素信号传导的功能尚不清楚。在虹鳟鱼的胚胎发育和早期骨骼肌生长过程中，对激活素受体信号通路表达进行了全面表征（RBT，Oncorhynchusmykiss）。虹鳟鱼是一种模型鲑鱼物种，已经经历了另外两轮的全基因组复制。少数基因在发育早期表达，大多数基因在整个发育过程中表达增加。尽管这些基因在孵化后骨骼肌中表现出明显升高的表达，但在RBT胚胎中活化素Ab的表达有限。激活素Aa1的CRISPR编辑和随后的减数分裂雌激素后代的产生表明，激活素Aa1的双等位基因破坏不会导致发育缺陷，如哺乳动物中激活素A的敲除所发生的。大多数雌核发育后代表现出纯合活化素Aa1基因型(野生型，帧内,或移码）源自马赛克创始人女性。该研究确定了在整个胚胎发育以及幼虫和幼鱼肌肉高生长期间重复的活化素同种关系中的专业化机制。获得的知识提供了对工程激活素受体信号通路的潜在可行基因靶向方法的见解，并确立了采用减数分裂雌核发育作为生产具有长世代时间的物种的纯合F1基因组编辑鱼的工具的可行性。比如鲑鱼。
