Role of Src family kinases and N-Myc in spermatogonial stem cell proliferation.
Spermatogonial stem cells are required for the initiation of spermatogenesis and the continuous production of sperm. In addition, they can acquire pluripotency and differentiate into derivatives of the three embryonic germ layers when cultured in the appropriate conditions. Therefore, understanding the signaling pathways that lead to self-renewal or differentiation of these cells is of paramount importance for the treatment of infertility, the development of male contraceptives, the treatment of testicular cancers, and ultimately for tissue regeneration. In this report, we studied some of the signaling pathways triggered by glial cell line-derived neurotrophic factor (GDNF), a component of the spermatogonial stem cell niche produced by the somatic Sertoli cells. As model systems, we used primary cultures of mouse spermatogonial stem cells, a mouse spermatogonial stem cell line and freshly isolated testicular tubules. We report here that GDNF promotes spermatogonial stem cell proliferation through activation of members of the Src kinase family, and that these kinases exert their action through a PI3K/Akt-dependent pathway to up-regulate N-myc expression. Thus, to proliferate, spermatogonial stem cells activate mechanisms that are similar to the processes observed in brain stem cells and lung progenitors.
Braydich-Stolle
Laura
L
Department of Biology, The University of Dayton, Dayton, OH 45469, USA.
Kostereva
Natalia
N
Dym
Martin
M
Hofmann
Marie-Claude
MC
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013093:Spermatogonia / Q000166:cytology*; D019061:src-Family Kinases / Q000378:metabolism*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D016271:Proto-Oncogene Proteins c-myc; D019061:src-Family Kinases