Analysis of cell cycle-related gene expression in postmitotic neurons: Selective induction of cyclin D1 during programmed cell death

Robert S. Freeman, Steven Estus, Eugene M. Johnson

Research output: Contribution to journalArticlepeer-review

547 Scopus citations

Abstract

Sympathetic neurons undergo RNA and protein synthesis-dependent programmed cell death when deprived of nerve growth factor. To test the hypothesis that neuronal programmed cell death is a consequence of conflicting growth signals which cause the inappropriate activation of cell cycle genes, we have analyzed cell cycle-related genes for their expression in postmitotic neurons. Surprisingly, many of these genes are expressed in neurons, although cdc2, cdk2, and cyclin A are not. During programmed cell death, the expression of most of these genes, including several cyclins and the Rb and p53 tumor suppressor genes, decreases similar to that of neuronal genes. In contrast, cyclin D1 expression is selectively induced in dying neurons. Cyclin Dl mRNA levels peak 15-20 hr after nerve growth factor withdrawal, concurrent with the time that neurons become committed to die. These results provide an extensive characterization of cell cycle gene expression in postmitotic neurons and provide the evidence for a gene induced during neuronal programmed cell death.

Original languageEnglish
Pages (from-to)343-355
Number of pages13
JournalNeuron
Volume12
Issue number2
DOIs
StatePublished - Feb 1994

Bibliographical note

Funding Information:
We thank Patricia A. Lampe, Patricia A. Osborne, and Jenny L. Columbo for their expert technical assistance. We also thank Dr. Charles Sherr for the mouse cyclin Dl plasmid. This work was supported by National Institutes of Health postdoctoral fellowship NS09294 (R. S. F.) and grants from the Washington University School of Medicine Alzheimer’s Disease Research Center and the American Paralysis Association.

ASJC Scopus subject areas

  • Neuroscience (all)

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