Biology subjects

Kurko, J.

Publications and source records attributed to Kurko, J..

8 recordsLinked to original sources

bioRxiv2025

Testicular gene expression patterns suggest a heterochronic shift underlying vgll3-mediated maturation age variation in Atlantic salmon

Heterochrony, or shifts in developmental timing, drives phenotypic diversity within and between species and shapes life history traits that can be selected for in changing environments which in turn promotes population resilience. Despite its importance, the molecular basis of heterochrony remains largely unknown. Mutations in "heterochronic genes" that regulate these processes can induce stable timing shifts, impacting important life history traits like pubertal timing. Heterochronic shifts in gene transcription are often tissue-specific and in mammals, for example, the testis shows the most pronounced heterochrony across species, especially during spermatogenesis. Age at maturity is a key adaptive trait across species, with vgll3, a Hippo pathway co-factor, as a main determinant in Atlantic salmon. The roles of vgll3 in maturation timing, adiposity, and energy storage are evolutionarily conserved across fish and mammals. Recent studies in salmon show vgll3 alleles; early (E) and late (L), affect reproductive gene expression, reinforcing its role in regulating developmental timing. This study examines whether vgll3 influences testicular heterochrony in Atlantic salmon by analyzing Hippo pathway-related gene expression in E and L genotypes. We observed heterochronic divergence in Hippo pathway gene transcription, indicating accelerated spermatogenesis-linked changes in the testes of vgll3*EE individuals. Since maturation in Atlantic salmon is closely tied to environmental changes, and the Hippo pathway acts as an environmental sensor, these findings suggest that Hippo-vgll3 shifts may also respond to environmental signals. This positions vgll3 as a heterochronic gene which is potentially affected by environmental changes (heterokairic), making it an ideal target for studying ecological adaptation linked to heterochrony.

developmental biology↗

bioRxiv2024

Hippo-vgll3 signaling may contribute to sex differences in Atlantic salmon maturation age via contrasting adipose dynamics

Sexual maturation in Atlantic salmon entails a transition in energy utilization, governed in part by genes and environmental stimuli in sex-specific manner. Salmon males require less energy, in the form of adiposity, to mature compared to females and typically mature younger. Maturation age is also influenced in a sex-dependent fashion by the vgll3 genotype (vestigial-like 3), a co-factor in the Hippo pathway. The underlying molecular processes of sex-dependent maturation age, and how they interplay with adiposity and vgll3 genotypes, have remained unknown. To elucidate the molecular mechanisms underlying sex- and genotype-specific maturation differences, we investigated the association of early (E) and late (L) maturation vgll3 alleles and the transcriptional expression of > 330 genes involved in the regulation of the Hippo pathway and sexual maturation, and related to molecular signals in brain, adipose tissue, and gonads. The strongest effect of vgll3 genotype was observed in adipose tissue for females and in brain for males, highlighting a sex-specific expression difference in the main association of vgll3 genotype. Genes related to ovarian development showed increased expression in vgll3*EE compared to vgll3*LL females. Additionally, vgll3*EE females compared to vgll3*EE males exhibited reduced markers of pre-adipocyte differentiation and lipolysis yet enhanced expression of genes related to adipocyte maturation and lipid storage. Brain gene expression further showed sex-specific expression signals for genes related to hormones and lipids, as well as tight junction assembly. Overall, these sex-specific patterns point towards a greater lipid storage and slower energy utilization in females compared to males. These results suggest that Hippo-dependent mechanisms may be important mediators of sex differences in maturation age in salmon.

genetics↗

bioRxiv2024

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

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.

genetics↗

bioRxiv2023

Gene co-expression patterns in Atlantic salmon adipose tissue provide a molecular link between seasonal changes, energy balance and age at maturity

Sexual maturation in many fishes requires a major physiological change that involves a rapid transition between energy storage and usage. In Atlantic salmon, this transition for the initiation of maturation is tightly controlled by seasonality and requires a high-energy status. Lipid metabolism is at the heart of this transition since lipids are the main energy storing molecules. The balance between lipogenesis (lipid accumulation) and lipolysis (lipid use) determines energy status transitions. A genomic region containing a transcription co-factor of the Hippo pathway, vgll3, is the main determinant of maturation timing in Atlantic salmon. Interestingly, vgll3 acts as an inhibitor of adipogenesis in mice and its genotypes are potentially associated with seasonal heterochrony in lipid storage and usage in juvenile Atlantic salmon. Here, we explored changes in expression of more than 300 genes directly involved in the processes of adipogenesis, lipogenesis and lipolysis, as well as the Hippo pathway in the adipose tissue of immature and mature Atlantic salmon with distinct vgll3 genotypes. We found molecular evidence consistent with a scenario in which immature males exhibiting vgll3 genotype specific seasonal direction of change in their lipid profiles. We also identified components of the Hippo signaling pathway as potential major drivers of vgll3 genotype specific differences in adipose tissue gene expression. This study demonstrates the importance of adipose gene expression patterns for directly linking environmental changes with energy balance and age at maturity through genetic factors bridging lipid metabolism, seasonality and sexual maturation.

physiology↗

bioRxiv2023

Seasonal and genetic effects on lipid profiles of juvenile Atlantic salmon

Seasonality can influence many physiological traits requiring optimal energetic capacity for life-history stage transitions. In Atlantic salmon, high-energy status is essential for the initiation of maturation. Atlantic salmon lipid reserves are predominantly found in the viscera and myosepta in the muscle while the liver is essential for maintaining lipid metabolism. A genomic study found a region including a transcription co-factor-coding gene, vgll3, linked to Atlantic salmon maturation timing, which acts as an inhibitor of adipogenesis in mice, and mediates maturation via condition factor in Atlantic salmon. Here we investigate the influence of season and vgll3 genotypes associating with early (EE) and late (LL) maturation on lipid profiles in the muscle and liver in juvenile Atlantic salmon. We reared Atlantic salmon for two years until the occurrence of sexually mature males and sampled muscle and liver at two time points: spring and autumn of the second year. We found no seasonal or genotype effect in lipid profiles in muscle of immature males and females. However, in the liver we did detect a triacylglycerol (TG) enrichment and a genotype specific direction of change in membrane lipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), from spring to autumn. Specifically, from spring to autumn membrane lipid concentrations increased in vgll3*EE individuals and decreased in vgll3*LL individuals. This could be explained with two possible scenarios 1) a seasonally more stable capacity of endoplasmic reticulum (ER) functions in vgll3*EE individuals compared to vgll3*LL individuals or 2) vgll3*LL individuals storing larger lipid droplets from spring to autumn in the liver compared to vgll3*EE individuals at the expense of ER capacity. This genotype specific seasonal direction of change in membrane lipid concentrations provides more indirect evidence that a mechanism linking vgll3 with lipid metabolism and storage exists. HighlightsO_LISeasonal lipid species profile separation in muscle and liver in juvenile Atlantic salmon C_LIO_LIGenotype specific direction of change of membrane lipids from spring to autumn C_LIO_LIIndirect evidence that a mechanism linking vgll3 with lipid metabolism and storage exists C_LI

evolutionary biology↗

bioRxiv2023

Genotype-specific variation in seasonal body condition at a large-effect maturation locus

O_LIOrganisms utilize varying lipid resource allocation strategies as a means to survive seasonal environmental changes and life-history stage transitions. In Atlantic salmon, a certain lipid threshold is needed to initiate sexual maturation. Because of this, an individuals maturation schedule may be affected by changes in temperature and food availability across the seasons that create natural fluctuations of lipid reserves. C_LIO_LIRecent studies have found a genome region, including the gene vgll3, that explains a large proportion of variation for size and age at maturity. Vgll3 encodes a transcription co-factor that acts as an inhibitor of adipogenesis in mice and also affects condition factor and other phenotypes in juvenile salmon. However, even with many studies investigating varying temperature effects, there is a lack of temporal studies examining the effects of seasonality on such phenotypes, nor have the effects of vgll3 genotype on condition factor and maturation in different temperatures at different life stages. C_LIO_LIHere, we investigate the influence of different larval and juvenile incubation temperatures, vgll3 genotype and their interactions on juvenile salmon phenotypes including body condition, and sexual maturation rate. We reared Atlantic salmon for 2 years in varying temperatures with an average 1.76 {degrees}C difference between warm and cold treatments in four different larval-juvenile phase treatment groups (Warm-Warm, Warm-Cold, Cold-Warm, and Cold-Cold) until the first occurrence of maturation in males. C_LIO_LIWe found no effect of larval temperature on the measured phenotypes or maturation rate, suggesting the occurrence of growth compensation over the course of the experiment. Agreeing with previous studies, an increased maturation rate was observed in individuals of the warm juvenile temperature treatment. C_LIO_LIIn addition, we observed differences in condition factor associated with vgll3 genotype, whereby vgll3*EE individuals (the genotype associated with early maturation) had a less variable condition factor across the seasons compared to the vgll3*LL (associated with late maturation) individuals. C_LIO_LIThis result suggests a vgll3 influence on resource acquisition and allocation strategies, possibly linked with the early maturation process, with individuals carrying the early maturation vgll3 genotype having a higher early maturation rate and a higher condition factor in the spring. C_LI

evolutionary biology↗

bioRxiv2020

Sex-specific lipid profiles in muscle of Atlantic salmon juveniles

Energy allocation in juvenile fish can have important implications for future life-history progression. Inherited and environmental factors determine when and where individuals allocate energy, and timely and sufficient energy reserves are crucial for reaching key life stages involved in the timing of maturation and sea migration. In Atlantic salmon, lipid reserves are predominantly found in the viscera and myosepta in the muscle and have been shown to play a key role in determining the timing of maturity. This life-history trait is tightly linked to fitness in many species and can be different between males and females, however, the details of relative energy allocation in juveniles of different sexes is not well understood. Therefore, the aim of this study was to investigate the effects of sex, genetics and environment during juvenile development of salmon on the amount and composition of their lipid reserves. To do so, juvenile salmon were fed one of two different lipid food contents during their first summer and autumn under common-garden conditions. Muscle lipid composition and concentrations were determined by thin layer chromatography. The muscle lipid class concentrations covaried negatively with body length and males showed higher concentrations than females for phosphatidylcholine, cholesterol, sphingomyelin, and triacylglycerol. This sex-specific difference in major lipid classes presents a new scope for understanding the regulation of lipids during juvenile development and gives direction for understanding how lipids may interact and influence major life-history traits in Atlantic salmon.

molecular biology↗

bioRxiv2019

Transcription profiles of age-at-maturity-associated genes suggest cell fate commitment regulation as a key factor in the Atlantic salmon maturation process

Despite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated chromosomal regions including genes vgll3, akap11 and six6, which have roles in adipogenesis, spermatogenesis and the hypothalamic-pituitary-gonadal (HPG) axis, respectively. Here, we determine expression patterns of these genes during salmon development and their potential molecular partners and pathways. Using Nanostring transcription profiling technology, we show development- and tissue-specific mRNA expression patterns for vgll3, akap11 and six6. Correlated expression levels of vgll3 and akap11, which have adjacent chromosomal location, suggests they may have shared regulation. Further, vgll3 correlating with arhgap6 and yap1, and akap11 with lats1 and yap1 suggests that Vgll3 and Akap11 take part in actin cytoskeleton regulation. Tissue-specific expression results indicate that vgll3 and akap11 paralogs have sex-dependent expression patterns in gonads. Moreover, six6 correlating with slc38a6 and rtn1, and Hippo signaling genes suggests that Six6 could have a broader role in the HPG neuroendrocrine and cell fate commitment regulation, respectively. We conclude that Vgll3, Akap11 and Six6 may influence Atlantic salmon maturation timing via affecting on adipogenesis and gametogenesis by regulating cell fate commitment and the HPG axis. These results may help to unravel general molecular mechanisms behind maturation.

genetics↗