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Melanocortin 4 receptor signaling and puberty onset regulation in Xiphophorus swordtails.
General and Comparative Endocrinology ( IF 2.1 ) Pub Date : 2020-05-26 , DOI: 10.1016/j.ygcen.2020.113521
Ruiqi Liu 1 , Kang Du 2 , Jenny Ormanns 1 , Mateus C Adolfi 2 , Manfred Schartl 3
Affiliation  

Fish of the genus Xiphophorus provide a prominent example of genetic control of male body size and reproductive tactics. In X. nigrensis and X. multilineatus, puberty onset and body length are determined by melanocortin 4 receptor (Mc4r) allelic and copy number variations which were proposed to fine-tune the signaling output of the system. Accessory protein Mrap2 is required for growth across species by affecting Mc4r signaling. The molecular mechanism how Mc4r signaling controls puberty regulation in Xiphophorus and whether the interaction with Mrap2 is also involved was so far unclear. Hence, we examined Mc4r and Mrap2 in X. nigrensis and X. multilineatus, in comparison to a more distantly related species, X. hellerii. mc4r and mrap2 transcripts co-localized in the hypothalamus and preoptic regions in large males, small males and females of X. nigrensis, with similar signal strength for mrap2 but higher expression of mc4r in large males. This overexpression is constituted by wild-type and one subtype of mutant alleles. In vitro studies revealed that Mrap2 co-expressed with Mc4r increased cAMP production but did not change EC50. Cells co-expressing the wild-type and one mutant allele showed lower cAMP signaling than Mc4r wild-type cells. This indicates a role of Mc4r alleles, but not Mrap2, in puberty signaling. Different from X. nigrensis and X. multilineatus, X. hellerii has only wild-type alleles, but also shows a puberty onset and body length polymorphism, despite the absence of mutant alleles. Like in the two other species, mc4r and mrap2 transcripts colocalized and mc4r is expressed at substantially higher levels in large males. This demonstrates that puberty and growth regulation mechanism may not be identical even within same genus.



中文翻译:

剑尾鱼中黑皮质素4受体信号转导和青春期发作调节。

Xiphophorus属的鱼类是对男性体型和生殖策略进行遗传控制的重要例子。在黑斑病菌X. nigrensis)多头弯曲杆菌X. multilineatus)中,青春期发作和体长是由黑皮质素4受体(Mc4r)等位基因和拷贝数变异决定的,提出该变异是为了微调系统的信号输出。辅助蛋白Mrap2是通过影响Mc4r信号在整个物种中生长所必需的。的分子机制MC4R信号控制青春期调控如何剑尾鱼以及是否相互作用Mrap2也参与了这么远不清楚。因此,我们在黑斑病菌(X. nigrensis)多发黑斑病菌X. multilineatus)中检查了Mc4r和Mrap2 ,与远物种X. hellerii相比MC4Rmrap2转录共定位在大男性,小男性和女性的下丘脑和视前区X. nigrensis,具有类似的信号强度mrap2但高表达MC4R在大男性。该过表达由突变型等位基因的野生型和一种亚型构成。体外研究表明,Mrap2与Mc4r共表达可增加cAMP产生,但不会改变EC50。共表达野生型和一个突变等位基因的细胞显示出比Mc4r野生型细胞更低的cAMP信号传导。这表明Mc4r等位基因(而非Mrap2)在青春期信号传导中的作用。与黑黑线虫X. nigrensis)多线黑线菌X. multilineatus)不同,尽管没有突变等位基因,但黑眼线虫X. hellerii)仅具有野生型等位基因,还显示青春期发作和体长多态性。像其他两个物种一样,mc4rmrap2转录本共定位,而mc4r在大雄性中的表达水平更高 这表明即使在同一属中,青春期和生长调节机制也可能不同。

更新日期:2020-05-26
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