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Published November 1991 | public
Journal Article

Co-expression of multiple neurotransmitter enzyme genes in normal and immortalized sympathoadrenal progenitor cells


We have examined the expression of mRNAs encoding five major neurotransmitter-synthesizing enzymes in MAH cells, a clonal cell line derived by retroviral immortalization of a rat embryonic sympathoadrenal progenitor cell. These mRNAs include tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), tryptophan hydroxylase (TpH), and glutamic acid decarboxylases (GADs) 1 and 2. We find that MAH cells express high levels of TH mRNA and low levels of ChAT and TpH mRNAs. Neither GAD1 nor GAD2 mRNAs are detectable using an RNase protection assay with a detection limit of less than one transcript per cell. A similar pattern of mRNA expression is observed in postnatal superior cervical ganglia, adrenal medulla, and in PC12 cells. Transmitter synthesis and accumulation assays indicate that MAH cells can synthesize both catecholamines and acetylcholine. Thus the TH and ChAT mRNAs detected in these cells are likely to be translated into active enzyme. To corroborate these data obtained using MAH cells, we performed similar transmitter synthesis and accumulation assays on sympathoadrenal progenitors directly isolated from E14.5 fetal adrenal glands by fluorescence-activated cell sorting. These progenitor cells also synthesize and accumulate both catecholamines and acetylcholine, albeit to different extents than MAH cells. Both MAH cells and their nonimmortal counterparts are able to increase slightly their cholinergic function upon short-term exposure to CDF/LIF, a factor known to induce acetylcholine synthesis in postmitotic sympathetic neurons. Taken together, these data suggest that progenitor cells in the sympathoadrenal lineage acquire the ability to simultaneously transcribe several different neurotransmitter enzyme genes early in development, prior to their choice of final cell fate. At the same time, the progenitors possess receptors which regulate expression of these genes in response to environmental factors. This ability may permit the cells to choose from several different transmitter phenotypes in response to different environments, as they migrate through the embryo. The persistent transcription of these genes in adult cells, moreover, may in part account for the phenotypic plasticity of cells in this lineage.

Additional Information

© 1991 Academic Press, Inc. Accepted July 22, 1991. We thank Dr. Hiroyuki Nawa for help in isolating the ChAT genomic clone, Drs. Alan Tobin and Mark Erlander for providing GAD1 and GAD2 cDNAs, and Dr. James Stoll for providing the TpH cDNA. We especially thank Dr. Susan Birren and Ms. Adela Augsburger for their help in fetal adrenal gland dissections, and Shelley Diamond for cell sorting. We thank Dr. Paul Patterson for providing CDF/LIF and helpful advice and discussion, and Dr. Tetsuo Yamamori for help in setting up the transmitter synthesis assay. We are grateful to Steven Padilla for expert technical assistance and to Helen Walsh for help in preparation of the manuscript. This work was supported by NIH Grant NS23476, a grant from the Dysautonomia Foundation (to D.J.V.), a Sloan Foundation Fellowship, and an NSF Presidential Young Investigator Award (to D.J.A.) D.J.A. is an Assistant Investigator of the Howard Hughes Medical Institute. This paper is dedicated to the memory of the late Bibi Jentoft-Nilssen, an undergraduate who conducted preliminary experiments for this project.

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August 20, 2023
October 20, 2023