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
References
Jan 1, 1993·Developmental Biology·P RossiR Geremia
Jun 21, 1996·The Journal of Biological Chemistry·D M OrnitzM Goldfarb
Feb 2, 2000·Nature Genetics·P Blume-JensenT Hunter
Mar 16, 2000·The EMBO Journal·H KisselP Besmer
Aug 15, 2001·The Journal of Biological Chemistry·S DolciP Rossi
Aug 9, 2003·Blood·Linda A CairnsSergio Ottolenghi
Oct 8, 2004·The International Journal of Developmental Biology·Louise WillertonSarah Mackay
Feb 4, 2005·Endocrine Reviews·Ralph T Böttcher, Christof Niehrs
Apr 1, 2006·Science·Josephine BowlesPeter Koopman
Oct 24, 2006·Animal Reproduction Science·Xinyan Tang, Caiqiao Zhang
Jun 23, 2007·Endocrinology·Glenn MacLeanMartin Petkovich
Oct 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yuna KimBlanche Capel
Nov 27, 2007·Gene Expression Patterns : GEP·Pellegrino RossiRaffaele Geremia
Dec 20, 2007·Developmental Biology·Francesca LolicatoPaola Grimaldi
Dec 23, 2008·Cell Cycle·Manuela PellegriniSusanna Dolci
Jan 8, 2010·Molecular Biology of the Cell·Elisa CiraoloEmilio Hirsch
Jan 23, 2010·Nature Reviews. Cancer·Nicholas Turner, Richard Grose
Feb 9, 2010·PloS One·Manuela PellegriniPaola Grimaldi
Feb 18, 2010·Journal of Cell Science·Florencia BarriosSusanna Dolci
Sep 14, 2010·Developmental Cell·Josephine BowlesPeter Koopman
Aug 26, 2011·Molecular Biology of the Cell·Catherine R DegninWilliam A Horton
Mar 8, 2012·Endocrinology·Benoit SouquetGabriel Livera
Oct 5, 2012·Development·Cassy M SpillerJosephine Bowles
Dec 12, 2012·Development·Quan WuYumiko Saga
Jun 21, 2013·The International Journal of Developmental Biology·Katherine A EwenEwa Rajpert-De Meyts
Citations
Oct 13, 2015·Seminars in Cell & Developmental Biology·Susanna DolciMassimo De Felici
Apr 15, 2016·Organogenesis·Meng-Shao LaiBu-Miin Huang
Nov 7, 2016·Molecular and Cellular Endocrinology·M L TottyL J Spicer
Jun 9, 2017·Molecular Human Reproduction·Blair R McCallieMandy G Katz-Jaffe
Mar 5, 2016·Oncotarget·Paola De LucaAdriana De Siervi
Nov 25, 2017·Cell Cycle·Liangyu ZhaoZheng Li
Jul 23, 2019·Molecular Human Reproduction·Kun YuShou-Long Deng
Feb 1, 2020·Development·Silvana GuioliRobin Lovell-Badge
Apr 11, 2017·Biology of Reproduction·Ferhat UluYukiko Yamazaki
Jan 19, 2021·Journal of Ethnopharmacology·Jisheng WangBin Wang
Jan 15, 2021·Scientific Reports·Kasane Imura-KishiYoshiakira Kanai
Jan 8, 2021·Reproductive Biology and Endocrinology : RB&E·Maryam KhanehzadSeyed Mehdi Nourashrafeddin
Oct 28, 2020·Cell Proliferation·Fan YangRalph L Brinster
Aug 19, 2021·Journal of Gynecology Obstetrics and Human Reproduction·Neda SaebniaAhmad Reza Bahrami