ArticlePloS one2013
Signaling through the TGF beta-activin receptors ALK4/5/7 regulates testis formation and male germ cell development.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 100 citations in OpenAlex.
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- Sharks and rays have the oldest vertebrate sex chromosome with unique sex determination mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- VEGF-dependent testicular vascularisation involves MEK1/2 signalling and the essential angiogenesis factors, SOX7 and SOX17.BMC biology · 2024Article
- FGF-independent MEK1/2 signalling in the developing foetal testis is essential for male germline differentiation in mice.BMC biology · 2023Article
- From Enrico Sertoli to freemartinism: the many phases of the master testis-determining cell†.Biology of reproduction · 2023Review
- Testis exposure to unopposed/elevated activin AFrontiers in endocrinology · 2023Article
- Abundance ofFrontiers in immunology · 2023Article
- Behavior and Functional Roles of CD34International journal of molecular sciences · 2022Review
- Somatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B.Nature communications · 2022Article
- Crucial Convolution: Genetic and Molecular Mechanisms of Coiling during Epididymis Formation and Development in Embryogenesis.Journal of developmental biology · 2022Review
- The undescended testis in children and adolescents part 2: evaluation and therapeutic approach.Pediatric surgery international · 2022Review
- The Impact of Activin A on Fetal Gonocytes: Chronic Versus Acute Exposure Outcomes.Frontiers in endocrinology · 2022Article
- Activin receptor type IIB in rohu (Labeo rohita): molecular characterization, tissue distribution and immunohistochemical localization during different stages of gonadal maturation.Fish physiology and biochemistry · 2021Article
- A Potential Role for the Gsdf-eEF1α Complex in Inhibiting Germ Cell Proliferation: A Protein-Interaction Analysis in Medaka (Oryzias latipes) From a Proteomics Perspective.Molecular & cellular proteomics : MCP · 2021Article
- Influence of Nodal signalling on pluripotency factor expression, tumour cell proliferation and cisplatin-sensitivity in testicular germ cell tumours.BMC cancer · 2020Article
- Betaglycan (TβRIII) is a Key Factor in TGF-β2 Signaling in Prepubertal Rat Sertoli Cells.International journal of molecular sciences · 2019Article
- Article
- Molecular Mechanisms and Signaling Pathways Involved in Sertoli Cell Proliferation.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The developing testis provides an environment that nurtures germ cell development, ultimately ensuring spermatogenesis and fertility. Impacts on this environment are considered to underlie aberrant germ cell development and formation of germ cell tumour precursors. The signaling events involved in testis formation and male fetal germ cell development remain largely unknown. Analysis of knockout mice lacking single Tgfβ family members has indicated that Tgfβ's are not required for sex determination. However, due to functional redundancy, it is possible that additional functions for these ligands in gonad development remain to be discovered. Using FACS purified gonadal cells, in this study we show that the genes encoding Activin's, TGFβ's, Nodal and their respective receptors, are expressed in sex and cell type specific patterns suggesting particular roles in testis and germ cell development. Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGFβ signaling is required for testis cord formation during the critical testis-determining period. We also show that signaling through the Activin/NODAL receptors, ALK4 and ALK7 is required for promoting differentiation of male germ cells and their entry into mitotic arrest. Finally, our data demonstrate that Nodal is specifically expressed in male germ cells and expression of the key pluripotency gene, Nanog was significantly reduced when signaling through ALK4/5/7 was blocked. Our strategy of inhibiting multiple Activin/NODAL/TGFβ receptors reduces the functional redundancy between these signaling pathways, thereby revealing new and essential roles for TGFβ and Activin signaling during testis formation and male germ cell development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.