A Caltech Library Service

Environmental Influences in the Development of Neural Crest Derivatives: Glucocorticoids, Growth Factors, and Chromaffin Cell Plasticity

Doupe, Allison J. and Landis, Story C. and Patterson, Paul H. (1985) Environmental Influences in the Development of Neural Crest Derivatives: Glucocorticoids, Growth Factors, and Chromaffin Cell Plasticity. Journal of Neuroscience, 5 (8). pp. 2119-2142. ISSN 0270-6474. PMCID PMC6565296. doi:10.1523/jneurosci.05-08-02119.1985.

[img] PDF - Published Version
Creative Commons Attribution.


Use this Persistent URL to link to this item:


The neural crest gives rise to three major adrenergic cell types: sympathetic principal neurons, adrenal chromaffin cells, and small intensely fluorescent (SIF) cells. All of these derivatives synthesize and store catecholamines, but they differ in numerous other characteristics. SIF cells appear intermediate in phenotype between the other two. We have examined the role of several environmental factors in the differentiation of sympathetic principal neurons and adrenal chromaffin cells. In previous studies of young rat adrenal chromaffin cells in dissociated cell culture, differentiated characteristics such as the presence of the enzyme phenylethanolamine N-methyltransferase (PNMT), epinephrine (E) synthesis, and large catecholamine storage vesicles were not well maintained. Here we describe long-term culture of chromaffin cells which, in the presence of micromolar glucocorticoid, maintained all of these characteristics. In addition, chromaffin cells of a variety of ages were found to be dependent on glucocorticoid for long-term survival in culture. In the absence of glucocorticoid, many adrenal chromaffin cells from neonatal rats could be rescued by nerve growth factor (NGF) administration. They extended neurites, as previously described by Unsicker and colleagues (Unsicker, K., B. Krisch, U. Otten, and H. Thoenen (1978) Proc. Natl. Acad. Sci. U.S.A. 75: 3498–3502). In contrast to previous studies, however, with long-term exposure to NGF these cells became indistinguishable from mature sympathetic neurons, as judged by the following morphological and biochemical criteria: increased cell size and loss of intense CA fluorescence in their cell bodies; acquisition of characteristic neuronal ultrastructure, including morphologically specialized synapses; loss of chromaffin granules, PNMT, and E synthesis; and acquisition of neuron markers, including tetanus toxin labeling and immunoreactivity to neurofilament protein. This conversion to neurons was markedly enhanced by addition of a non-neuronal cell conditioned medium (CM) containing a neurite-promoting factor, which acted by increasing the NGF responsiveness of the chromaffin cells. Even chromaffin cells from adult rats, which are known to grow few processes in response to NGF alone, became neuronal in the presence of this CM plus NGF. While converting to neurons, adrenal chromaffin cells transiently assumed an intermediate phenotype resembling type I SIF cells, which suggests particular developmental relationships between the different cell types of the sympathoadrenal lineage.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Additional Information:© 1985 Society for Neuroscience. For the first six months after publication SfN’s license will be exclusive. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received September 4, 1984: Revised December 7, 1984: Accepted December 7, 1984. A J. D. was a member of and supported in part by the Harvard University Society of Fellows, and in part by the Insurance Medical Scientist Scholarship Fund and the Prudential Life Insurance Co. S. C. L. is an Established Investigator of the American Heart Association, supported in part by the Massachusetts Affiliate. P H. P. was a Rita Allen Foundation Scholar and a McKnight Foundation Neuroscience Development Awardee. We wish to thank Doreen MacDowell and John Fredieu for expert technical assistance and Wendy Brooks, Joe Gagl1ard1, and Shirley Wilson for manuscript preparation. We also wish to thank Torn Fox for the generous use of his HPLC equipment, and Jane Dodd, Jim Huettner, Tom Jessel!, Bill Matthew, and Eve Wol1nsky for helpful discussions of the manuscript.
Funding AgencyGrant Number
Harvard University Society of FellowsUNSPECIFIED
Insurance Medical Scientist Scholarship FundUNSPECIFIED
Prudential Life Insurance Co.UNSPECIFIED
American Heart Association, Massachusetts AffiliateUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
McKnight FoundationUNSPECIFIED
Issue or Number:8
PubMed Central ID:PMC6565296
Record Number:CaltechAUTHORS:20160517-100104280
Persistent URL:
Official Citation:Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity AJ Doupe, SC Landis, and PH Patterson The Journal of Neuroscience, 1 August 1985, 5(8):2119-2142
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67153
Deposited By: Ruth Sustaita
Deposited On:17 May 2016 17:33
Last Modified:11 Nov 2021 00:28

Repository Staff Only: item control page