Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF

• Published in: Science (American Association for the Advancement of Science) Vol. 287; no. 5457; pp. 1489 - 1493
• Main Authors: Meng, Xiaojuan, Lindahl, Maria, Hyvönen, Mervi E., Parvinen, Martti, de Rooij, Dirk G., Hess, Michael W., Raatikainen-Ahokas, Anne, Sainio, Kirsi, Rauvala, Heikki, Lakso, Merja, Pichel, José G., Westphal, Heiner, Saarma, Mart, Sariola, Hannu
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 25-02-2000; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Adults; Anatomy; Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Cycle; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell nucleus; Cell physiology; Cellular biology; Cobalt - metabolism; Drosophila Proteins; Embryos; Female; Females; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Targeting; General aspects; Genes; Germ cells; Glial Cell Line-Derived Neurotrophic Factor; Glial Cell Line-Derived Neurotrophic Factor Receptors; Individualized Instruction; Male; Males; Mice; Mice, Transgenic; Mitosis; Molecular and cellular biology; Molecules; Nerve Growth Factors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neuroglia; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Rodents; Sertoli cells; Sertoli Cells - cytology; Sertoli Cells - physiology; Spermatogenesis; Spermatogonia; Spermatogonia - cytology; Spermatogonia - drug effects; Stem cells; Stem Cells - cytology; Testes; Testicular Neoplasms - pathology; Testis - anatomy & histology; Transgenic animals; Vitamin A - pharmacology; Cell proliferation; Sertoli cell; Glial cell; Spermatogenesis; Stem cell; Rodentia; Cell cell interaction; Cell differentiation; Testicle; Carcinogenesis; Biological activity; Germ cell tumor; Neurotrophic factor; Regeneration; Vertebrata; Mammalia; Mouse; Animal; Germ line; Spermatogonia; Glial cell line derived neurotrophic factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.287.5457.1489

The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line-derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonial cells that include the stem cells for spermatogenesis. Gene-targeted mice with one GDNF-null allele show depletion of stem cell reserves, whereas mice overexpressing GDNF show accumulation of undifferentiated spermatogonia. They are unable to respond properly to differentiation signals and undergo apoptosis upon retinoic acid treatment. Nonmetastatic testicular tumors are regularly formed in older GDNF-overexpressing mice. Thus, GDNF contributes to paracrine regulation of spermatogonial self-renewal and differentiation.