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FGF independent MEK1/2 signalling is essential for male germline development in mice [somatic cell]

ABSTRACT: FGF independent MEK1/2 signalling is essential for male germline development in mice [somatic cell]

PROVIDER: PRJNA914333 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22834366_1.fastq.gz	Fastqsanger.gz
	SRR22834366_2.fastq.gz	Fastqsanger.gz
	SRR22834367_1.fastq.gz	Fastqsanger.gz
	SRR22834367_2.fastq.gz	Fastqsanger.gz
	SRR22834368_1.fastq.gz	Fastqsanger.gz

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FGF independent MEK1/2 signalling is essential for male germline development in mice [somatic cell]

Project description:Germline development provides the founding cells for spermatogenesis and oogenesis in males and females, respectively. Disrupted germline differentiation or compromised testis development can lead to subfertility or infertility and are strongly associated with testis cancer in humans. In mice, SRY and SOX9 induce expression of a range of genes, including Fgf9, that promote Sertoli cell differentiation and testis development. FGF9 is also thought to promote male germline differentiation but the pathway through which it signals is unknown. As FGFs signal through Mitogen-Activated Protein Kinases (MAPKs) in other tissues, we explored whether FGF9 regulates male germline development through MAPK by inhibiting either FGF or MEK1/2 signalling in fetal testis cultures from embryonic day (E)12.5, immediately after gonadal sex determination and testis cord formation, but prior to male germline commitment. Inhibition of MEK1/2 disrupted mitotic arrest, dysregulated a broad range of male germline development genes and prevented the upregulation of key male germline markers DPPA4 and DNMT3L. In contrast, when FGF signalling was inhibited, the male germline specific transcriptional program and the expression of male germline markers DPPA4 and DNMT3L were unaffected, and the germ cells entered mitotic arrest normally. While male germline development was not disrupted by FGF inhibition, a significant number of genes were commonly altered after 24h of FGF or MEK1/2 inhibition including genes involved in maintenance germline stem cells, Nodal signalling, proliferation, and germline cancer. Together, these data demonstrate a novel and essential role for MEK1/2 signalling in male germline differentiation, but a surprisingly limited role for FGF signalling. Our data strongly indicate that additional ligands act through MEK1/2 to promote male germline differentiation and highlight a need for further mechanistic understanding of male germline development.

2023-11-21 | GSE221458 | GEO

FGF independent MEK1/2 signalling is essential for male germline development in mice [germ cell]

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FGF independent MEK1/2 signalling is essential for male germline development in mice [germ cell]

Project description:FGF independent MEK1/2 signalling is essential for male germline development in mice [germ cell]

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FGF-independent MEK1/2 signalling in the developing foetal testis is essential for male germline differentiation in mice

Project description: Not available

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Transcription profiling of Xenopus embryos in which fibroblast growth factor (FGF) signalling was inhibited by two different dominant negative FGF receptors

Project description:Genes regulated by the fibroblast growth factor (FGF) signalling pathway were indentified in the early development of the amphibian Xenopus laevis by comparing gene expression in control embryos and embryos in which FGF signalling was inhibited by two different dominant negative FGF receptors.

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Enhancer activation by FGF signalling during otic induction

Project description:We report that FGF exposure of sensory progenitors (pPPR) leads to rapid deposition of active chromatin marks H3K27ac near hundreds of FGF-responsive, otic-epibranchial progenitor (OEP) genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elements controlling OEP gene expression in time and space and define a unique transcription factor signature likely to control their activity. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.

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Enhancer activation by FGF signalling during otic induction

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Transcription profiling of human embryonic stem cells treated with BMP4 in chemically-defined medium, with and without inhibitors of Activin and FGF signalling to investigate the induction of extra-embryonic tissue differentiation by BMP signalling

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Transcription profiling of Hex+Cxcr4+ differentiating mouse embryonic stem cells to study a role for FGF signalling in the generation of Anterior Definitive Endoderm

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