Role of PI3K and MAPK in male germ cell differentiation and development

Both FGF9 and KL signal through tyrosine kinase receptors (and thus probably partially shared signal transduction pathways), yet they exert opposite effects on meiotic differentiation in postnatal spermatogonia, FGF9 acting as a meiotic inhibiting substance and KL acting as a promoter of the differentiation process. The aim of this thesis is to understand the differences in intracellular signaling elicited by this two antagonistic growth factors and the downstream cascade of events that lead to RA/KL-mediated induction of meiotic entry and FGF9- mediated inhibition of the same mechanism. To this end, using mouse spermatogonia obtained through several enzymatic digestions of testis from 7 dpp CD-1 mice (when KITpositive cells compared), we first characterized which subtypes of FGFs receptors are expressed in these cells and we investigated whether activation of NODAL signaling is involved in FGF9 action in post-natal spermatogonia as it was described for fetal germ cells. Finally, since the molecular signaling by which FGF9 negatively control meiotic entry of spermatogonia is not known, we tried to understand the signaling pathway activated by this growth factor on post-natal male germ cells comparing its effect to the previously studied KLsignaling.