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The Journal of Neuroscience, February 15, 1998, 18(4):1440-1448
Synergistic Effects of Schwann- and Muscle-Derived Factors on Motoneuron Survival Involve GDNF and Cardiotrophin-1 (CT-1)
Vilma Arce1, *, Richard A. Pollock1, *, Jean-Marc Philippe1, Diane Pennica2, Christopher E. Henderson1 and Odile deLapeyrière1 1 Institut National de la Santé et de la Recherche Médicale (INSERM) U.382, Developmental Biology Institute of Marseille (Centre National de la Recherche Scientifique-INSERM-Université de la Méditerranée), Campus de Luminy, 13288 Marseille, France, and 2 Department of Molecular Oncology, Genentech Incorporated, South San Francisco, California 94080
The survival of central neurons depends on multiple neurotrophic factors produced by different cell types. We demonstrate that media conditioned by muscle and Schwann cell lines show strong synergistic effects on survival of purified embryonic day 14.5 rat motoneurons in culture. Different lines of evidence implicate glial cell line-derived neurotrophic factor (GDNF) and cardiotrophin-1 (CT-1) in this synergy. Their expression in the environment of the motoneuron is compartmentalized: gdnf transcripts are expressed principally in Schwann cell lines, whereas ct-1 mRNA is present in myotubes. Blocking antibodies to GDNF inhibit the trophic activity of Schwann cell line-conditioned media by 75%, whereas CT-1 antibodies diminish the myotube-derived activity by 46%. CT-1 and GDNF act synergistically to enhance motoneuron survival in vitro. In vivo, individual motoneurons coexpress both GDNF and CT-1 receptor components. GDNF and CT-1, therefore, are major components of the trophic support provided by the Schwann and muscle cells, respectively. The possibility that they act together on individual motoneurons suggests that the motoneuron must integrate distinct signals from different cellular partners when deciding whether to die or to survive.
Key words: motoneuron survival; neurotrophic factors; synergy; GDNF; cardiotrophin-1; CNTF; Schwann cells; muscle cells; blocking antibodies; in situ hybridization
Copyright © 1998 Society for Neuroscience 0270-6474/98/1841440-09$05.00/0
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