Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF

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 undifferen...

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Veröffentlicht in:	Science (American Association for the Advancement of Science) 2000-02, Vol.287 (5457), p.1489-1493
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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.
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.287.5457.1489