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Sympathetic neuroblasts undergo a developmental switch in trophic dependence

Birren, Susan J. and Lo, Liching and Anderson, David J. (1993) Sympathetic neuroblasts undergo a developmental switch in trophic dependence. Development, 119 (3). pp. 597-610. ISSN 0950-1991.

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Sympathetic neurons require NGF for survival, but it is not known when these cells first become dependent on neurotrophic factors. We have examined in vitro mitotically active sympathetic neuroblasts immuno-isolated from different embryonic stages, and have correlated this functional data with the expression of neurotrophin receptor mRNAs in vivo. Cells from E14.5 ganglia are supported by neurotrophin-3 (NT-3) in a serum-free medium, but not by NGF; NT-3 acts as a bona fide survival factor for these cells and not simply as a mitogen. By birth, sympathetic neurons are well-supported by NGF, whereas NT-3 supports survival only weakly and at very high doses. This change in neurotrophin-responsiveness is correlated with a reciprocal switch in the expression of trkC and trkA mRNAs by sympathetic neuroblasts in vivo. These data suggest that neurotrophic factors may control neuronal number at earlier stages of development than previously anticipated. They also suggest that the acquisition of NGF-dependence may occur, at least in part, through the loss of receptors for these interim survival factors.

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Anderson, David J.0000-0001-6175-3872
Additional Information:© 1993 The Company of Biologists Limited. Accepted 30 July 1993. We thank Pantelis Tsouflas and Luis Parada for providing trkA, trkB and trkC probes, George Yancopoulos for providing recombinant NT-3, Pat Cohen and Rochelle Diamond for help with cell sorting and members of the Anderson laboratory for their constructive suggestions during the course of this work. We are grateful to Jane Dodd for advice on non-radioactive in situ hybridization and for providing monoclonal antibody B2. We also thank Andrew Groves, Mahendra Rao and Paul Patterson for their critical comments on the manuscript. This work was supported by NIH grant NS23476 and by a PEW Faculty Fellowship in Neuroscience. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute.
Funding AgencyGrant Number
PEW Faculty Fellowship in NeuroscienceUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:neuroblast, sympathetic neuroblast, NGF, neurotrophic factor
Issue or Number:3
Record Number:CaltechAUTHORS:20120301-074441528
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29537
Deposited By: Tony Diaz
Deposited On:20 Mar 2012 22:39
Last Modified:30 Mar 2020 22:20

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