A pituitary gene network linking vgll3 to regulators of sexual maturation in male Atlantic salmon

Ahi, Ehsan Pashay; Sinclair-Waters, Marion; Donner, Iikki; Primmer, Craig R.

doi:10.1016/j.cbpa.2022.111337

Cited by 7 publications

(6 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The only interacting partner of Hippo with lower expression in vgll3*EE individuals was a paralog encoding an immediate early gene (IEG) called early growth factor-1 ( egr1a ). Strikingly, egr1 is known to be a major factor mediating socially-induced sexual maturation in fish hypothalamus (Maruska and Fernald 2011), and also we have recently found its differential expression as part of a pituitary gene network associated with vgll3 -depenendent transcriptional regulation of gonadotropins (Ahi et al . 2023).…”

Section: Discussionmentioning

confidence: 99%

“…alleles associated with early (E) and late (L) maturation and the expression patterns of a number of crucial reproductive axis genes (Ahi et al 2022(Ahi et al , 2024a. The anticipation that vgll3 genotype effects on reproductive axis genes may be modulated through divergent Hippo signaling pathway activation has been shown by gene co-expression network analysis (Ahi et al 2023). The Hippo pathway is rapidly emerging not only as a pivotal molecular signal governing sexual maturation in vertebrates (Kjaerner-Semb et al 2018;Sen Sharma et al 2019;Kurko et al 2020) but also as a regulator in the equilibrium between adipocyte proliferation and differentiation (Ahi et al 2024b).…”

Section: Recent Investigations In Atlantic Salmon Have Demonstrated A...mentioning

confidence: 99%

“…2022, 2024a). The anticipation that vgll3 genotype effects on reproductive axis genes may be modulated through divergent Hippo signaling pathway activation has been shown by gene co-expression network analysis (Ahi et al . 2023).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Pashay Ahi,

Verta,

Kurko

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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,vgll3also inhibits adipogenesis in mice. Recent studies in salmon revealed correlations betweenvgll3genotypes 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 differentvgll3 early(E) andlate(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 (mc4raandmc4rc) in individuals withearly(E) maturation genotypes ofvgll3before maturation development of testes. Moreover, we found components and interacting partners of Hippo pathway showing differential expression in brain of individuals withearly(E) andlate(L)vgll3genotypes 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Recent Investigations In Atlantic Salmon Have Demonstrated A...mentioning

confidence: 99%

See 1 more Smart Citation

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

Pashay Ahi,

Verta,

Kurko

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, VGLL3 regulates the expression of c-Jun, which can directly activate the transcription of YAP1, a major readout of the Hippo pathway [39,40] . As a critical regulator of glycose and glutamine metabolism, c-Jun is known to activate inflammatory pathways and its regulation by VGLL3 is dependent on the canonical Hippo pathway, suggesting again the presence of a feedback loop between the two pathways [40–43] . Therefore, there is a growing interest in understanding the potential crosstalk between the VGLL3 and Hippo pathways in regulating sexual dimorphism in autoimmunity, exemplified by studies showing that VGLL3 drives IFN-β1 expression in fibroblast-like synoviocytes of RA patients by inhibiting TAZ1 expression [37] .…”

Section: Vgll3 and Hippo – Interaction Of Nutrient-sensing Pathwaysmentioning

confidence: 99%

The immunometabolic function of VGLL3 and female-biased autoimmunity

Kennicott,

Liang

2024

Immunometabolism

View full text Add to dashboard Cite

Autoimmune diseases exhibit a pronounced yet unexplained prevalence among women. Vestigial-like family member 3 (VGLL3), a female-biased factor that promotes autoimmunity, has recently been discovered to assist cells in sensing and adapting to nutritional stress. This role of VGLL3 may confer a selective advantage during the evolution of placental mammals. However, the excessive activation of the VGLL3-mediated energy-sensing pathway can trigger inflammatory cell death and the exposure of self-antigens, leading to the onset of autoimmunity. These observations have raised the intriguing perspective that nutrient sensing serves as a double-edged sword in immune regulation. Mechanistically, VGLL3 intersects with Hippo signaling and activates multiple downstream, immune-associated genes that play roles in metabolic regulation. Understanding the multifaceted roles of VGLL3 in nutrient sensing and immune modulation provides insight into the fundamental question of sexual dimorphism in immunometabolism and sheds light on potential therapeutic targets for autoimmune diseases.

show abstract

“…Recent studies of one year old Atlantic salmon identified strong association between vgll3 early (E) and late (L) maturation alleles and the expression of key reproductive axis genes (Ahi, Sinclair-Waters, Moustakas-Verho, Jansouz, & Primmer, 2022). Gene co-expression network analysis predicted that the vgll3 genotype effects on reproductive axis genes are likely to be mediated by differential activation of the Hippo signaling pathway (Ahi, Sinclair-Waters, Donner, & Primmer, 2023). The Hippo pathway is emerging as a key molecular signal not only in controlling sexual maturation in vertebrates (Kjærner-Semb et al, 2018; Kurko et al, 2020; Sen Sharma, Vats, & Majumdar, 2019), but also in balancing adipocyte proliferation versus differentiation, and the activity of Yap1 (a major transcription co-factor of the Hippo pathway) has been found to be indispensable during adipogenesis (Ardestani, Lupse, & Maedler, 2018).…”

Section: Introductionmentioning

confidence: 99%

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

Ahi,

Verta,

Kurko

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

A pituitary gene network linking vgll3 to regulators of sexual maturation in male Atlantic salmon

Cited by 7 publications

References 65 publications

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

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

The immunometabolic function of VGLL3 and female-biased autoimmunity

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

Contact Info

Product

Resources

About