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bioRxiv · 10.1101/2024.03.18.585557

A salmon fish model reveals genetic signals in brain associated with early maturation

Pashay Ahi, E.·Verta, J.-P.·Kurko, J.·Ruokolainen, A.·Singh, P.·Debes, P. V.·Erkinaro, J.·Primmer, C. R.
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Abstract

Emerging evidence suggests a link between adiposity and early maturation, potentially impacting hormonal signaling pathways governing puberty timing. Fish models have proven invaluable in studying these processes, given their genetic and physiological similarities to humans. In Atlantic salmon, in addition to being linked with environmental shifts and lipid reserves, the timing of sexual maturation also has a strong genetic basis. A gene encoding a co-factor of Hippo pathway, vgll3, is a major determinant of maturation timing in salmon, and the same gene was found to be associated with maturation timing in humans. Intriguingly, vgll3 also inhibits adipogenesis in mice. Recent studies in salmon revealed correlations between vgll3 genotypes and reproductive axis gene expression, possibly modulated through the Hippo signaling pathway. The Hippo pathway is known for its role in sexual maturation and adipogenesis and responds to environmental cues such as dietary fat and temperature. In this study, we employed a custom gene expression panel in male Atlantic salmon with different vgll3 early (E) and late (L) maturation genotypes testing components of this pathway in brain at immature and mature stages. We found increased brain expression of a major Hippo pathway kinase (lats1b) and melanocortin receptor encoding genes (mc4ra and mc4rc) in individuals with early (E) maturation genotypes of vgll3 before maturation development of testes. Moreover, we found components and interacting partners of Hippo pathway showing differential expression in brain of individuals with early (E) and late (L) vgll3 genotypes prior to maturation. This could indicate extensive and complex roles of Hippo pathway in brain processes required for preparing for [the onset of] maturation at upstream of reproductive axis. This study elucidates molecular mechanisms underpinning early maturation, and for the first time in fish, offering insights into detecting it at molecular level in brain before visible gonadal changes occur.

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Pashay Ahi, E., Verta, J.-P., Kurko, J., Ruokolainen, A., Singh, P., Debes, P. V., Erkinaro, J., Primmer, C. R.. 2024-03-19. A salmon fish model reveals genetic signals in brain associated with early maturation. https://doi.org/10.1101/2024.03.18.585557

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