The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells

• Published in: PloS one Vol. 8; no. 4; p. e59431
• Main Authors: Dovere, Lisa, Fera, Stefania, Grasso, Margherita, Lamberti, Dante, Gargioli, Cesare, Muciaccia, Barbara, Lustri, Anna Maria, Stefanini, Mario, Vicini, Elena
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22-04-2013; Public Library of Science (PLoS)
• Subjects: Actin; Actin Cytoskeleton; Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Actins; Actins - metabolism; Animals; Axon guidance; Biological activity; Biology; Boyden chamber; Cell adhesion; Cell Adhesion Molecules; Cell Adhesion Molecules - metabolism; Cell culture; Cell lines; Cell migration; Cell Movement; Cell Movement - drug effects; Cell self-renewal; Cells (biology); Cellular Biology; Cytoskeleton; Embryology; Gametes; Glial Cell Line-Derived Neurotrophic Factor; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Glial Cell Line-Derived Neurotrophic Factor Receptors; Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism; Histology; Humans; Life Sciences; Ligands; Male; Mammals; Mice; Mice, Inbred C57BL; Microfilament Proteins; Microfilament Proteins - metabolism; Muscle proteins; Neuronal-glial interactions; Phosphoproteins; Phosphoproteins - metabolism; Progenitor cells; Progeny; Proteins; Rats; Rodents; Spermatogenesis; Spermatogonia; Spermatogonia - cytology; Stem Cell Niche; Stem cell transplantation; Stem Cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Tubules; Vasodilator-stimulated phosphoprotein; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059431

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.