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Role of Glial Cell Line‐Derived Neurotrophic Factor in Germ‐Line Stem Cell Fate
Author(s) -
BRAYDICHSTOLLE LAURA,
NOLAN COURTNEY,
DYM MARTIN,
HOFMANN MARIECLAUDE
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1336.010
Subject(s) - glial cell line derived neurotrophic factor , numb , stem cell , biology , neurotrophic factors , microbiology and biotechnology , notch signaling pathway , sertoli cell , endocrinology , signal transduction , spermatogenesis , receptor , genetics
A bstract : The overall goal of this study is to unravel the role(s) played by glial cell line‐derived neurotrophic factor (GDNF) in the fate of spermatogonial stem cells. There is great interest in the biology of spermatogonial stem cells, or A single spermatogonia, because of their importance in the treatment of infertility, the development of contraceptives, and the understanding of the etiology of testicular cancer, particularly seminoma. In the mouse, spermatogonial stem cells express GFRα‐1, the receptor for GDNF, and respond to this growth factor in vivo and in vitro . GDNF is produced by the adjacent Sertoli cells, which are part of the germ‐line stem cell niche in vertebrates. We specifically isolated GFRα‐1‐positive spermatogonia using an immunomagnetic bead technique. We then stimulated the cells with 100 ng/mL of rGDNF for 10 hours; unstimulated cells served as negative controls. Microarray analysis, immunocytochemistry, and Western blotting revealed that Numb, a regulator of the Notch pathway, is upregulated by GDNF in spermatogonial stem cells. There are indications that in rats, mice, and humans, the Notch pathway promotes spermatogonial differentiation. We observed that an increase in Numb expression is concomitant with Notch degradation in these cells. Thus, through Numb, GDNF might inhibit differentiation and allows the maintenance of the stem cell pool in the mouse seminiferous epithelium.