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, reinforcing the antagonistic effect of these two growth factors on the meiotic fate of male germ cells.

Tassinari, V., Campolo, F., Cesarini, V., Todaro, F., DOLCI IANNINI, S., Rossi, P. (2015). 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, 6, e1688-e1688 [10.1038/cddis.2015.56].

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

DOLCI IANNINI, SUSANNA;ROSSI, PELLEGRINO
2015-03-12

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, reinforcing the antagonistic effect of these two growth factors on the meiotic fate of male germ cells.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/16
English
Con Impact Factor ISI
fibroblast growth factor 9; kit ligand; transforming growth factor beta superfamily; cripto; nodal; erk1/2; pi3k; akt; signal transduction; spermatogonia; meiosis; spermatogenesis; cell cycle; differentiation; stem cells.
Finanziato con fondi MIUR (Prin 2010C8ERKX_003, Prin 2009FW5SP3_001, and Firb RBAP109BLT_004)
Tassinari, V., Campolo, F., Cesarini, V., Todaro, F., DOLCI IANNINI, S., Rossi, P. (2015). 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, 6, e1688-e1688 [10.1038/cddis.2015.56].
Tassinari, V; Campolo, F; Cesarini, V; Todaro, F; DOLCI IANNINI, S; Rossi, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/110787
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