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PMID: 10688798 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of cell fate decision of undifferentiated spermatogonia by GDNF.

Science (New York, N.Y.) ·Vol. 287 ·No. 5457 ·2000-02-25 ·Pages 1489-93

Meng X, Lindahl M, Hyvönen ME, Parvinen M, de Rooij DG, Hess MW, Raatikainen-Ahokas A, Sainio K, Rauvala H, Lakso M, Pichel JG, Westphal H, Saarma M, Sariola H

Abstract

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.

MeSH Terms

Animals Apoptosis/drug effects Cell Cycle Cell Differentiation/drug effects Cobalt/metabolism Drosophila Proteins Female Gene Expression Gene Targeting Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Male Mice Mice, Transgenic Mitosis Nerve Growth Factors Nerve Tissue Proteins/genetics,physiology Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases/genetics,metabolism Sertoli Cells/cytology,physiology Spermatogenesis Spermatogonia/cytology,drug effects Stem Cells/cytology Testicular Neoplasms/pathology Testis/anatomy & histology Vitamin A/pharmacology

Chemicals

Drosophila Proteins Gdnf protein, mouse Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Nerve Growth Factors Nerve Tissue Proteins Proto-Oncogene Proteins Vitamin A cobalt ammonium complex Cobalt Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila

Authors & Affiliations

14 authors, click to expand affiliations / ORCID

Meng X

Research Programs of Developmental Biology, Molecular Neurobiology, Electron Microscopy Unit, Institute of Biotechnology, Viikki Biocenter, Finland.

Lindahl M

Hyvönen M E

Parvinen M

de Rooij D G

Hess M W

Raatikainen-Ahokas A

Sainio K

Rauvala H

Lakso M

Pichel J G

Westphal H

Saarma M

Sariola H

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.287.5457.1489

Published

2000-02-25

Pages

1489-93

Language

English

Region

United States

NLM ID

0404511

Subset

External Links

PubMed source DOI: 10.1126/science.287.5457.1489 View journal details

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Regulation of cell fate decision of undifferentiated spermatogonia by GDNF.

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