Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development DOI Creative Commons
Isabelle Stévant, Elisheva Abberbock, Meshi Ridnik

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract Gonadal sex determination relies on tipping a delicate balance involving the activation and repression of several transcription factors signalling pathways. This is likely mediated by numerous non-coding regulatory elements that shape sex-specific transcriptomic programs. To explore dynamics these in detail, we performed paired time-series chromatin accessibility assays pre-granulosa Sertoli cells throughout their development embryo, making use new existing mouse reporter lines. Regulatory were associated with putative target genes linkage analysis, this was complemented verified experimentally using promoter capture Hi-C. We identified factor motifs enriched along occupancy, pinpointing LHX9/EMX2 as potentially critical regulators ovarian development. Variations DNA sequence are to be responsible for many unexplained cases individuals Differences Sex Development. Teaser Multiomics analysis revealed gonadal determination.

Language: Английский

Reference genome provide insights into sex determination of silver aworana (Osteoglossum bicirrhosum) DOI Creative Commons
Yi Liu, Chao Bian, Ka Yan

et al.

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 29, 2025

Silver arowana (Osteoglossum bicirrhosum) is a basal fish species with sexual monomorphism, while its sex determination mechanism has been poorly understood, posing significant challenge to captive breeding efforts. We constructed two high-quality chromosome-level genome assemblies for both female and male silver arowana, scaffold N50 values over 10 Mb. Combining re-sequencing data of 109 individuals, we identified female-specific region, which was localized in non-coding i.e., around 26-kb upstream foxl2 gene (encoding forkhead box L2). Its strong interaction the neighboring on same chromosome suggests as candidate sex-related arowana. subsequently propose complex network process acting central contributor. Transcriptome sequencing gonads support our hypothesis that regulation can be influenced by spatial proximity fragment, thereby promoting ovarian function or inhibiting testicular stimulate gonadal differentiation. Furthermore, found chromosomes homomorphic potentially recent origin, linkage disequilibrium analysis proved minor recombination suppression. These results taken together serve crucial foundation conducting extensive investigations evolution differentiation sex-determining mechanisms, well emergence development various fishes.

Language: Английский

Citations

0
Gonadal sex determination in vertebrates: rethinking established mechanisms DOI
Dagmar Wilhelm, Aitana Perea-Gómez, Axel H. Newton

et al.

Development, Journal Year: 2025, Volume and Issue: 152(6)

Published: March 15, 2025

ABSTRACT Sex determination and differentiation are fundamental processes that not only essential for fertility but also influence the development of many other organs, hence, important species diversity survival. In mammals, sex is determined by inheritance an X or a Y chromosome from father. The harbours testis-determining gene SRY, it has long been thought its absence sufficient ovarian development. Consequently, pathway treated as default pathway, in sense ovaries do have need female-determining factor. Recently, factor identified mouse master regulator Interestingly, this scenario was predicted early 1983. Review, we discuss model 1983, how mechanisms genes currently known to be mammals changed supported model, finally, reflect on what these findings might mean vertebrates.

Language: Английский

Citations

0
Unveiling the role of FOXL2 in female differentiation and disease: a comprehensive review DOI Creative Commons
Jia He,

Zican Wang,

Lici Yang

et al.

Biology of Reproduction, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Abstract Ovarian differentiation relies on the accurate and orderly expression of numerous related genes. Forkhead box protein L2 (FOXL2) is one earliest ovarian markers transcription factors. In sex determination, FOXL2 maintains female pathway by inhibiting male genes, including SOX9 SF1. addition, promotes synthesis follicle-stimulating hormone anti-Müllerian to support follicle development. Mutations in are associated with reproductive diseases. A comprehensive in-depth study provides novel strategies for diagnosis treatment such This review discusses mechanism maintenance, synthesis, disease occurrence reveals role as a central factor development fertility maintenance. will serve reference identifying targets other regulatory factors interacting determination

Language: Английский

Citations

0
FOXL2 drives the differentiation of supporting gonadal cells in early ovarian development DOI Creative Commons

Laura Danti,

Karolina Lundin,

Petra Nedeczey-Ruzsák

et al.

Reproductive Biology and Endocrinology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 18, 2025

Abstract Background Forkhead box L2 ( FOXL2 ) is a transcription factor from the forkhead family primarily expressed in pituitary, ovaries, and eyelids. Human mutations cause blepharophimosis, ptosis, epicanthus inversus syndrome (BPES), which can be associated with primary ovarian insufficiency, indirectly linked differences of sex development (DSD). Animal studies have shown crucial role that plays development, function, maintenance ovary as well determination. However, specific early human somatic cell largely unknown. Methods In this study, we utilised CRISPR/Cas9 genome activation previously published in-house 14-day gonadal differentiation protocol to study . Results Our results demonstrate downregulates coelomic epithelial markers GATA4 LHX9 , female RSPO1 WNT4 male SOX9 NR0B1 DHH The differentially genes were mostly Kyoto encyclopaedia genomes (KEGG) pathways relating adhesion molecules gene ontology (GO) extracellular matrix junction formation. Furthermore, comparative analysis existing single RNA sequencing data vivo-derived samples elucidated initiates downregulation UPK3B at day 6. By 8, ARX GATA2 are transiently upregulated by induction then downregulated LGR5 TSPAN8 OSR1 TAC1 become upregulated. Conclusions These findings suggest facilitates exit differentiating cells epithelium initially drives them towards transitional identity before progressing into supporting gonadal-like cells. significantly advance our understanding normal used basis elucidate pathological underlying BPES.

Language: Английский

Citations

0
Obox1 deficiency impairs fertility in female mice DOI Creative Commons

Li Wu,

Jiacheng Shen, Zhenzhen Hou

et al.

Fundamental Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Divergent regulatory element programs steer sex-specific supporting cell differentiation along mouse gonadal development DOI Creative Commons
Isabelle Stévant, Elisheva Abberbock, Meshi Ridnik

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract Gonadal sex determination relies on tipping a delicate balance involving the activation and repression of several transcription factors signalling pathways. This is likely mediated by numerous non-coding regulatory elements that shape sex-specific transcriptomic programs. To explore dynamics these in detail, we performed paired time-series chromatin accessibility assays pre-granulosa Sertoli cells throughout their development embryo, making use new existing mouse reporter lines. Regulatory were associated with putative target genes linkage analysis, this was complemented verified experimentally using promoter capture Hi-C. We identified factor motifs enriched along occupancy, pinpointing LHX9/EMX2 as potentially critical regulators ovarian development. Variations DNA sequence are to be responsible for many unexplained cases individuals Differences Sex Development. Teaser Multiomics analysis revealed gonadal determination.

Language: Английский

Citations

0