TGF-β superfamily signaling in testis formation and early male germline development

Young, Julia; Wakitani, Shoichi; Loveland, Kate

doi:10.1016/j.semcdb.2015.10.029

Cited by 85 publications

(66 citation statements)

References 135 publications

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“…TGF-β signal is present in foetal and neonatal developing testis and required for GC development2223. BMP4, a member of the TGF-β superfamily, is essential for the PGC formation from initially sexually indifferent germline cells24. BMP4 promotes iPS cell differentiation into male GCs25.…”

Section: Discussionmentioning

confidence: 99%

CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling

Fang

Wei

et al. 2017

Sci Rep

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Previous studies have shown that CD61 (integrin-β3) promotes the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into germ-like cells. However, the mechanism remains unclear. In this study, we showed that overexpression of CD61 in canine adipose-derived mesenchymal stem cells (cADMSCs) promotes their differentiation into primordial germ cell (PGC)-like cells. Quantitative real-time PCR, immunocytochemistry and western blot detected higher levels of PGC-specific markers in CD61-overexpressed cADMSCs compared with those in control cells. Moreover, phosphorylation of Smad2, a downstream mediator of transforming growth factor beta (TGF-β), was increased in CD61-overexpressed cADMSCs than that in control cells. However, the expression of PGC-specific markers was downregulated in cADMSCs treated with a TGF-β inhibitor. These results suggested that CD61 could induce cADMSCs to differentiate into PGC-like cells by relying on the activation of TGF-β pathway. ADMSCs possess a considerable potential in treating the infertility of rare animal species.

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Section: Discussionmentioning

confidence: 99%

CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling

Fang

Wei

et al. 2017

Sci Rep

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“…The TGFB family comprises many members, including TGFB1-3, ACTIVIN and NODAL that signal through the activin-like kinases (ALK)-4, -5 and -7 to regulate target gene transcription (Young et al 2015). The chemical inhibitor SB431542 blocks ALK-4, -5 and -7 and is not a specific inhibitor of NODAL signalling, as it also blocks TGFB1-3 and ACTIVIN signalling.…”

Section: Discussionmentioning

confidence: 99%

Critical role of Emx2 in the pluripotency – differentiation transition in male gonocytes via regulation of FGF9/NODAL pathway

Zhang

et al. 2016

Reproduction

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Emx2 deletion impairs the growth and maintenance of the genital ridge. However, its role in subsequent germ cell differentiation during embryonic stages is unknown. Using a tamoxifen-inducible Cre-loxP mouse model (Emx2 flox/flox , Cre-ER TM , hereafter called as Emx2 knockdown), we showed that germ cell differentiation was impaired in Emx2-knockdown testes. Representative characteristics of male germ cell differentiation, including a reduced ability to form embryonic germ (EG) cell colonies in vitro, down-regulation of pluripotency markers and G1/G0 arrest, did not occur in Emx2-knockdown testes. Furthermore, FGF9 and NODAL signalling occurred at abnormally high levels in Emx2-knockdown testes. Both blocking FGF9 signalling with SU5402 and inhibiting NODAL signalling with SB431542 allowed germ cells from Emx2-knockdown testes to differentiate in vitro. Therefore, EMX2 in somatic cells is required to trigger germ cell differentiation in XY foetuses, posterior to its previously reported role in the growth and maintenance of the genital ridge.

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“…The transforming growth factor-β (TGF-β) superfamily contains activin, inhibin, bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), and TGF-β homodimeric proteins [57][58][59] . Smad4 serves as a crucial mediator of upstream signals in the TGF-β/Smad signaling pathway upon TGF-βs stimulation.…”

Section: The Tgf-β/smad Signaling Pathwaymentioning

confidence: 99%

“…Similarly, the activated AMPK signaling pathway also mediated 17β-estradiol inhibition on boar SCs proliferation, which would be abolished by compound C treatment. Zhang et al administrated 10 μM of 17β-estradiol on boar SCs and observed inhibition of miR-1285 expression 59 . Recently, they clarified that miR-1285 can downregulate α2AMPK mRNA and protein level.…”

Section: Scs Proliferationmentioning

confidence: 99%

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

2019

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The functions of Sertoli cells in spermatogenesis have attracted much more attention recently. Normal spermatogenesis depends on Sertoli cells, mainly due to their influence on nutrient supply, maintenance of cell junctions, and support for germ cells’ mitosis and meiosis. Accumulating evidence in the past decade has highlighted the dominant functions of the MAPK, AMPK, and TGF-β/Smad signaling pathways during spermatogenesis. Among these pathways, the MAPK signaling pathway regulates dynamics of tight junctions and adherens junctions, proliferation and meiosis of germ cells, proliferation and lactate production of Sertoli cells; the AMPK and the TGF-β/Smad signaling pathways both affect dynamics of tight junctions and adherens junctions, as well as the proliferation of Sertoli cells. The AMPK signaling pathway also regulates lactate supply. These signaling pathways combine to form a complex regulatory network for spermatogenesis. In testicular tumors or infertile patients, the activities of these signaling pathways in Sertoli cells are abnormal. Clarifying the mechanisms of signaling pathways in Sertoli cells on spermatogenesis provides new insights into the physiological functions of Sertoli cells in male reproduction, and also serves as a pre-requisite to identify potential therapeutic targets in abnormal spermatogenesis including testicular tumor and male infertility.

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TGF-β superfamily signaling in testis formation and early male germline development

Cited by 85 publications

References 135 publications

CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling

CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling

Critical role of Emx2 in the pluripotency – differentiation transition in male gonocytes via regulation of FGF9/NODAL pathway

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

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