The age at which Atlantic salmon reaches sexual maturity shows a strong hereditary component associated with the vgll3a locus. The role of Vgll3 in maturation has remained unknown in vertebrates until recently, when it has been linked to pleiotropic roles in killifish, both delaying male maturation and affecting lifespan by protecting against cancer. As Atlantic salmon has two vgll3 paralogs, where only vgll3a has been associated with sexual maturation, it may provide a suitable model for studying the maturation-specific function of vgll3, as the other paralog may buffer for pleiotropic roles of vgll3. To address this, we used CRISPR/Cas9 to generate fish highly mutated in the vgll3a gene. We monitored their maturation and crossed highly mutated crispants to generate two year-classes of complete loss-of-function. All groups were reared under environmental conditions triggering early maturation in one-year-old males. We found a clear difference in the proportion of sexually maturing or mature fish between the different genotypes: in all experiments significantly fewer vgll3a-/- males entered puberty and reached final maturation compared to vgll3a+/- and vgll3a+/+ males. Furthermore, loss of vgll3a resulted in lower frequencies of maturation also in females. We conclude that Vgll3a stimulates maturation and that its complete removal significantly reduced maturation rates in both sexes in Atlantic salmon. Our findings also identify vgll3a as the causative gene in the locus associated with age at sexual maturity. Together, our findings support a new role for Vgll3 in initiating puberty in vertebrates and identifying salmon as a promising model for functional studies regarding the timing of sexual maturation.
Kjaerner-Semb, E., Fraser, T. W. K., Vogelsang, P., Skaftnesmo, K., Ayllon, F., Edvardsen, R. B., Braathen, S., Norberg, B., Fjelldal, P. G., Andersson, E., Schulz, R. W., Wargelius, A.
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