GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells

Mayumi Jijiwa, Kumi Kawai, Jun Fukihara, Akari Nakamura, Masaki Hasegawa, Chikage Suzuki, Tomoko Sato, Atsushi Enomoto, Naoya Asai, Yoshiki Murakumo, Masahide Takahashi

研究成果: Article査読

58 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)365-374
ページ数10
ジャーナルGenes to Cells
13
4
DOI
出版ステータスPublished - 04-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 細胞生物学

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