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GDNF‐mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells
Author(s) -
Jijiwa Mayumi,
Kawai Kumi,
Fukihara Jun,
Nakamura Akari,
Hasegawa Masaki,
Suzuki Chikage,
Sato Tomoko,
Enomoto Atsushi,
Asai Naoya,
Murakumo Yoshiki,
Takahashi Masahide
Publication year - 2008
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2008.01171.x
Subject(s) - glial cell line derived neurotrophic factor , biology , microbiology and biotechnology , neurotrophic factors , receptor tyrosine kinase , signal transduction , tyrosine phosphorylation , stem cell , tyrosine , phosphorylation , gdnf family of ligands , endocrinology , receptor , genetics , biochemistry
Well‐organized spermatogenesis, including the maintenance of spermatogonial stem cells (SSCs), is indispensable for continuous male fertility. Signaling by glial cell line‐derived neurotrophic factor (GDNF) via the RET/GDNF family receptor α1 (GFRα1) receptor complex is essential for self‐renewal of murine SSCs and may also regulate their differentiation. When phosphorylated, tyrosine 1062 in RET presents a binding site for the phosphotyrosine‐binding domains of several adaptor and effector proteins that are important for activation of a variety of intracellular signaling pathways. In this study, we investigated the role of signaling via RET tyrosine 1062 in spermatogenesis using RET Y1062F knockin mice (Y1062F mice), in which tyrosine 1062 was replaced with phenylalanine. Homozygous Y1062F mice showed marked atrophy of testes due to reduced production of germ cells. RET‐expressing spermatogonia in seminiferous tubules of homozygous Y1062F mice decreased after postnatal day (P) 7 and germ cells were almost undetectable by P21. These phenomena appeared to be due to a lack of SSC self‐renewal and inability to maintain the undifferentiated state. Our findings suggest that RET signaling via tyrosine 1062 is essential for self‐renewal of SSCs and regulation of their differentiation.