The Niche-Derived Glial Cell Line-Derived Neurotrophic Factor (GDNF) Induces Migration of Mouse Spermatogonial Stem/Progenitor Cells |
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| Authors: | Lisa Dovere Stefania Fera Margherita Grasso Dante Lamberti Cesare Gargioli Barbara Muciaccia Anna Maria Lustri Mario Stefanini Elena Vicini |
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| Institution: | 1. Fondazione Pasteur Cenci Bolognetti, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences - Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.; 2. Centre for Integrative Biology, University of Trento, Trento, Italy.; 3. Department of Biology, University of Rome Tor Vergata, Rome, Italy.; University of Bern, Switzerland, |
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| 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. |
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