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The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization [Mouse]

ABSTRACT: Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele (gdf6X). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3, the mRNA decay activator zfp36l2 as a new GDF6 signaling target.

ORGANISM(S): Mus musculus

PROVIDER: GSE233995 | GEO | 2024/11/19

REPOSITORIES: GEO

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The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization [Human]

Project description:Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele (gdf6X). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3, the mRNA decay activator zfp36l2 as a new GDF6 signaling target.

2024-11-19 | GSE233992 | GEO

Chromosome conformation capture (Hi-C) of the turquoise killifish

Project description:This approach was used to increase the continuity of the killifish genome, and assess the relative distance of specific genes from the sex locus.

2024-03-06 | GSE218971 | GEO

The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-19 | GSE233997 | GEO

Project description:Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNAseq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.

| S-EPMC11320354 | biostudies-literature

Project description:Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNA-seq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterised, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNA-seq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasises the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.

| S-EPMC10979842 | biostudies-literature

Protocol for whole-brain immunostaining of the turquoise killifish after tissue clearing.

Project description:Distribution of cells and proteins in whole organs, such as the brain, can provide another level of insight into molecular and cellular functions. Here, we describe a whole-brain immunostaining method using the turquoise killifish, an emerging model for aging research. We optimized a protocol for tissue clearing and whole-brain immunostaining to the turquoise killifish brain. This protocol provides a comprehensive procedure from brain dissection to whole-brain imaging and image processing. For complete details on the use and execution of this protocol, please refer to Eunjeong Do (2020) and Lee et al. (2021).

| S-EPMC8176364 | biostudies-literature

Widespread sex dimorphism across single-cell transcriptomes of adult African turquoise killifish tissues.

Project description:The African turquoise killifish (Nothobranchius furzeri), the shortest-lived vertebrate that can be bred in captivity, is an emerging model organism for aging research. Here, we describe a multitissue, single-cell gene expression atlas of female and male blood, kidney, liver, and spleen. We annotate 22 cell types, define marker genes, and infer differentiation trajectories. We find pervasive sex-dimorphic gene expression across cell types. Sex-dimorphic genes tend to be linked to lipid metabolism, consistent with clear differences in lipid storage in female vs. male turquoise killifish livers. We use machine learning to predict sex using single-cell gene expression and identify potential markers for molecular sex identity. As a proof of principle, we show that our atlas can be used to deconvolute existing bulk RNA sequencing (RNA-seq) data to obtain accurate estimates of cell type proportions. This atlas can be a resource to the community that could be leveraged to develop cell-type-specific expression in transgenic animals.

| S-EPMC10842523 | biostudies-literature

Circular RNAs in the ageing African turquoise killifish

Project description:In this work we took 9 samples from brain and 6 samples from muscle of the African turquoise killifish (Nothobranchius furzeri) at 3.5, 8.5 and 14 weeks. Total RNA was sequenced and circRNAs were detected.

2019-07-31 | GSE134065 | GEO

The African Turquoise Killifish Genome Provides Insights into Evolution and Genetic Architecture of Lifespan.

Project description:Lifespan is a remarkably diverse trait ranging from a few days to several hundred years in nature, but the mechanisms underlying the evolution of lifespan differences remain elusive. Here we de novo assemble a reference genome for the naturally short-lived African turquoise killifish, providing a unique resource for comparative and experimental genomics. The identification of genes under positive selection in this fish reveals potential candidates to explain its compressed lifespan. Several aging genes are under positive selection in this short-lived fish and long-lived species, raising the intriguing possibility that the same gene could underlie evolution of both compressed and extended lifespans. Comparative genomics and linkage analysis identify candidate genes associated with lifespan differences between various turquoise killifish strains. Remarkably, these genes are clustered on the sex chromosome, suggesting that short lifespan might have co-evolved with sex determination. Our study provides insights into the evolutionary forces that shape lifespan in nature.

| S-EPMC4684691 | biostudies-literature

Sperm cryopreservation and in vitro fertilization techniques for the African turquoise killifish Nothobranchius furzeri.

Project description:Over the last decade, the African turquoise killifish, Nothobranchius furzeri, has emerged as an important model system for the study of vertebrate biology and ageing. Propagation of laboratory inbred strains of Nothobranchius furzeri, such as GRZ, however, can pose challenges due to the short window of fertility, the efforts and space requirements involved in continuous strain maintenance, and the risks of further inbreeding. The current method for long term strain preservation relies on arrest of embryos in diapause. To create an alternative for long term maintenance, we developed a robust protocol to cryopreserve and revive sperm for in vitro fertilization (IVF). We tested a variety of extender and activator buffers for sperm IVF, as well as cryoprotectants to achieve practical long-term storage and fertilization conditions tailored to this species. Our protocol enabled sperm to be preserved in a cryogenic condition for months and to be revived with an average of 40% viability upon thawing. Thawed sperm were able to fertilize nearly the same number of eggs as natural fertilization, with an average of ~ 25% and peaks of ~ 55% fertilization. This technical advance will greatly facilitate the use of N. furzeri as a model organism.

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