Neurotrophins regulate sequential changes in neurotrophin receptor expression by sympathetic neuroblasts
We have examined the mechanisms controlling the induction of the two NGF receptors, trkA and p75, in proliferating neuroblasts immuno-isolated from thoracolumbar embryonic sympathetic ganglia. Contrary to prior studies, we find that induction of p75 follows rather than precedes that of trkA; this late induction is consistent with the fact that p75 functions at relatively late stages of sympathetic development. trkA induction is apparently not controlled by a cell-intrinsic mechanism. Rather, this receptor is induced by environmental signals including NT-3, which also acts as an interim survival factor for these neuroblasts, trkA induction by NT-3 is consequent to its promotion of mitotic arrest, as anti-mitotic drugs also efficiently induce trkA. p75 expression is induced in trkA-expressing cells by NGF. Thus, the development of sympathetic neurons involves sequential actions of different neurotrophins, which also regulate the expression of their own and each other's receptors.
© 1994 by Cell Press. Received 16 September 1994, Revised 21 October 1994, Available online 22 April 2004. Correspondence should be addressed to D. J. A. We thank Susan Birren for her contributions to the early stages of this work and for helpful discussions, and Rochelle Diamond for expert assistance with cell sorting. We are also grateful to Louis Reichardt for generously providing antibody to trkA in advance of publication and to George Yancopoulos and Regeneron, Inc. for providing NT-3 and CNTF. This work was supported by a grant from the NIH. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.