title: The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.
abstract: In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF), a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.
authors.affiliation: Fondazione Pasteur Cenci Bolognetti, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences - Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Dovere
authors.forename: Stefania
authors.initials: S
authors.lastname: Fera
authors.forename: Margherita
authors.initials: M
authors.lastname: Grasso
authors.forename: Dante
authors.initials: D
authors.lastname: Lamberti
authors.forename: Cesare
authors.initials: C
authors.lastname: Gargioli
authors.forename: Barbara
authors.initials: B
authors.lastname: Muciaccia
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Lustri
authors.forename: Mario
authors.initials: M
authors.lastname: Stefanini
authors.forename: Elena
authors.initials: E
authors.lastname: Vicini
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D013093:Spermatogonia / Q000166:cytology*; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein