Platelet-derived growth factor receptor beta-subtype regulates proliferation and migration of gonocytes.
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 beta-subtype (PDGFR-beta) and that during the same time period, the Sertoli cells express PDGF-B and PDGF-D, both ligands for PDGFR-beta. Inhibition of the PDGFR-beta 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-beta ligands are chemotactic for gonocytes. These data suggest that PDGFR-beta 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.
Basciani
Sabrina
S
Department of Medical Physiopathology, Sapienza University, Policlinico Umberto I, 00161 Rome, Italy.
De Luca
Gabriele
G
Dolci
Susanna
S
Brama
Marina
M
Arizzi
Mario
M
Mariani
Stefania
S
Rosano
Giuseppe
G
Spera
Giovanni
G
Gnessi
Lucio
L
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013076:Sperm Count; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta