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Department of Medical Physiopathology (S.B., M.B., M.A., S.M., G.S., L.G.), University of Rome La Sapienza; Department of Environment and Primary Prevention (G.D.L.), Istituto Superiore di Sanità, 00161 Rome, Italy; Department of Medical Sciences (S.B., G.R.), Cardiovascular Research Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Roma, Tosinvest Sanità, 00187 Rome, Italy; and Department of Public Health and Cell Biology (S.D.), Section of Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy
Address all correspondence and requests for reprints to: Lucio Gnessi, M.D., Ph.D., Department of Medical Physiopathology, Sapienza University, Policlinico Umberto I, 00161 Rome, Italy. E-mail: lucio.gnessi{at}uniroma1.it.
Proliferation and migration of gonocytes, the precursors of spermatogonial stem cells, to the germline niche in the basal membrane of the seminiferous tubules, are two crucial events that take place between postnatal d 0.5 (P0.5) and P5.0 in the mouse and involve a selection of the cells that are committed to the germline stem cells lineage. Here we show that from embryonic d 18.0 (E18) and up to P5, the gonocytes express platelet-derived growth factor (PDGF) receptor β-subtype (PDGFR-β) and that during the same time period, the Sertoli cells express PDGF-B and PDGF-D, both ligands for PDGFR-β. Inhibition of the PDGFR-β tyrosine kinase activity during the first five postnatal days provokes a profound reduction of gonocyte number through inhibition of their proliferation and induction of apoptosis. Moreover, we found that PDGFR-β ligands are chemotactic for gonocytes. These data suggest that PDGFR-β activation has the remarkable capability to drive the selection, survival, and migration of the gonocytes from the center of the seminiferous tubules to the testicular germline niche on the basal membrane.
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