Fgf9 inhibition of meiotic differentiation in spermatogonia is mediated by Erk-dependent activation of Nodal-Smad2/3 signaling and is antagonized by Kit Ligand

Cell Death & Disease
V TassinariP Rossi

Abstract

Both fibroblast growth factor 9 (Fgf9) and Kit Ligand (Kl) signal through tyrosine kinase receptors, yet they exert opposite effects on meiotic differentiation in postnatal spermatogonia, Fgf9 acting as a meiosis-inhibiting substance and Kl acting as a promoter of the differentiation process. To understand the molecular mechanisms that might underlie this difference, we tried to dissect the intracellular signaling elicited by these two growth factors. We found that both Fgf9 and Kl stimulate Erk1/2 activation in Kit+ (differentiating) spermatogonia, even though with different time courses, whereas Kl, but not Fgf9, elicits activation of the Pi3k-Akt pathway. Sustained Erk1/2 activity promoted by Fgf9 is required for induction of the autocrine Cripto-Nodal-Smad2/3 signaling loop in these cells. Nodal signaling, in turn, is essential to mediate Fgf9 suppression of the meiotic program, including inhibition of Stra8 and Scp3 expression and induction of the meiotic gatekeeper Nanos2. On the contrary, sustained activation of the Pi3k-Akt pathway is required for the induction of Stra8 expression elicited by Kl and retinoic acid. Moreover, we found that Kl treatment impairs Nodal mRNA expression and Fgf9-mediated Nanos2 induction, rein...Continue Reading

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Citations

Oct 13, 2015·Seminars in Cell & Developmental Biology·Susanna DolciMassimo De Felici
Jun 9, 2017·Molecular Human Reproduction·Blair R McCallieMandy G Katz-Jaffe
Jul 23, 2019·Molecular Human Reproduction·Kun YuShou-Long Deng
Jan 8, 2021·Reproductive Biology and Endocrinology : RB&E·Maryam KhanehzadSeyed Mehdi Nourashrafeddin
Aug 19, 2021·Journal of Gynecology Obstetrics and Human Reproduction·Neda SaebniaAhmad Reza Bahrami

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Methods Mentioned

BETA
transfection
nuclear translocation
PCR
Assay

Software Mentioned

ImageJ

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