title: Microarray Analysis Reveals Increased Transcriptional Repression and Reduced Metabolic Activity but Not Major Changes in the Core Apoptotic Machinery during Maturation of Sympathetic Neurons.
abstract: Postnatal maturation of the neurons whose main phenotype and basic synaptic contacts are already established includes neuronal growth, refinement of synaptic contacts, final steps of differentiation, programmed cell death period (PCD) etc. In the sympathetic neurons, postnatal maturation includes permanent end of the PCD that occurs with the same time schedule in vivo and in vitro suggesting that the process could be genetically determined. Also many other changes in the neuronal maturation could be permanent and thus based on stable changes in the genome expression. However, postnatal maturation of the neurons is poorly studied. Here we compared the gene expression profiles of immature and mature sympathetic neurons using Affymetrix microarray assay. We found 1310 significantly up-regulated and 1151 significantly down-regulated genes in the mature neurons. Gene ontology analysis reveals up-regulation of genes related to neuronal differentiation, chromatin and epigenetic changes, extracellular factors and their receptors, and cell adhesion, whereas many down-regulated genes were related to metabolic and biosynthetic processes. We show that termination of PCD is not related to major changes in the expression of classical genes for apoptosis or cell survival. Our dataset is deposited to the ArrayExpress database and is a valuable source to select candidate genes in the studies of neuronal maturation. As an example, we studied the changes in the expression of selected genes Igf2bp3, Coro1A, Zfp57, Dcx, and Apaf1 in the young and mature sympathetic ganglia by quantitative PCR and show that these were strongly downregulated in the mature ganglia.
authors.affiliation: Department of Gene Technology, Tallinn University of Technology Tallinn, Estonia.
authors.forename: Mikk
authors.initials: M
authors.lastname: Raba
authors.affiliation: Department of Gene Technology, Tallinn University of Technology Tallinn, Estonia.
authors.forename: Jaan
authors.initials: J
authors.lastname: Palgi
authors.affiliation: Biomedicum Functional Genomics Unit, Biomedicum Helsinki, University of Helsinki Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Lehtivaara
authors.affiliation: Department of Gene Technology, Tallinn University of TechnologyTallinn, Estonia; Institute of Biotechnology, University of HelsinkiHelsinki, Finland.
authors.forename: Urmas
authors.initials: U
authors.lastname: Arumäe
keywords: maturation; microarray; nerve growth factor; programmed cell death; sympathetic neurons