Platelet-derived growth factor receptor beta-subtype regulates proliferation and migration of gonocytes

Sabrina Basciani; Gabriele De Luca; Susanna Dolci; Marina Brama; Mario Arizzi; Stefania Mariani; Giuseppe Rosano; Giovanni Spera; Lucio Gnessi

doi:10.1210/en.2008-0349

Platelet-derived growth factor receptor beta-subtype regulates proliferation and migration of gonocytes

Endocrinology. 2008 Dec;149(12):6226-35. doi: 10.1210/en.2008-0349. Epub 2008 Aug 7.

Authors

Sabrina Basciani¹, Gabriele De Luca, Susanna Dolci, Marina Brama, Mario Arizzi, Stefania Mariani, Giuseppe Rosano, Giovanni Spera, Lucio Gnessi

Affiliation

¹ Department of Medical Physiopathology, Sapienza University, Policlinico Umberto I, 00161 Rome, Italy.

PMID: 18687785
DOI: 10.1210/en.2008-0349

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Apoptosis / drug effects
Apoptosis / physiology
Benzamides
Blotting, Western
Cell Movement / drug effects
Cell Movement / physiology*
Cell Proliferation*
Female
Imatinib Mesylate
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Phosphorylation / drug effects
Piperazines / pharmacology
Platelet-Derived Growth Factor / genetics
Platelet-Derived Growth Factor / metabolism
Proto-Oncogene Proteins c-sis / genetics
Proto-Oncogene Proteins c-sis / metabolism
Pyrimidines / pharmacology
Receptor, Platelet-Derived Growth Factor beta / genetics
Receptor, Platelet-Derived Growth Factor beta / metabolism
Receptor, Platelet-Derived Growth Factor beta / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Sertoli Cells / cytology
Sertoli Cells / metabolism
Sperm Count
Spermatozoa / cytology*
Spermatozoa / metabolism
Testis / cytology
Testis / drug effects
Testis / metabolism

Substances

Benzamides
Piperazines
Platelet-Derived Growth Factor
Proto-Oncogene Proteins c-sis
Pyrimidines
Imatinib Mesylate
Receptor, Platelet-Derived Growth Factor beta