Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF-Reference-Cited by-全球学者库

Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF

Published:2000-02-25 Issue:5457 Volume:287 Page:1489-1493
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Meng Xiaojuan¹,Lindahl Maria²,Hyvönen Mervi E.¹,Parvinen Martti³,de Rooij Dirk G.⁴,Hess Michael W.⁵,Raatikainen-Ahokas Anne¹,Sainio Kirsi¹,Rauvala Heikki⁶,Lakso Merja⁶,Pichel José G.⁷,Westphal Heiner⁸,Saarma Mart²,Sariola Hannu¹

Affiliation:

1. Research Programs of Developmental Biology,

2. Molecular Neurobiology,

3. Department of Anatomy, University of Turku, FIN-20520 Turku, Finland.

4. Department of Cell Biology, University Medical Center Utrecht, AZU-RM G02.525, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.

5. Electron Microscopy Unit, Institute of Biotechnology, Viikki Biocenter, Post Office Box 56 (Street address: Viikinkaari 9),

6. Transgenic Unit, Institute of Biotechnology and Department of Biosciences, Post Office Box 56, FIN-00014 University of Helsinki, Finland.

7. Unidad de Investigación, Hospital de Mérida, Polı́gono Nueva Ciudad s/n, 06800 Mérida, Badajoz, Spain.

8. National Institute of Child Health and Human Development, Building 6B, Room 413, Bethesda, MD 20892–2790, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference49 articles.

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