title: Glia-induced neuronal differentiation by transcriptional regulation.
abstract: There is increasing evidence that different phases of brain development depend on neuron-glia interactions including postnatal key events like synaptogenesis. To address how glial cells influence synapse development, we analyzed whether and how glia-derived factors affect gene expression in primary cultures of immunoisolated rat retinal ganglion cells (RGCs) by oligonucleotide microarrays. Our results show that the transcript pattern matched the developmental stage and characteristic properties of RGCs in vitro. Glia-conditioned medium (GCM) and cholesterol up- and downregulated a limited number of genes that influence the development of dendrites and synapses and regulate cholesterol and fatty acid metabolism. The oligonucleotide microarrays detected the transcriptional regulation of neuronal cholesterol homeostasis in response to GCM and cholesterol treatment. Surprisingly, our study revealed neuronal expression and glial regulation of matrix gla protein (Mgp). Together, our results suggest that glial cells promote different aspects of neuronal differentiation by regulating transcription of distinct classes of genes.
authors.affiliation: Department of Neurotransmission/Neuroendocrine Secretion, Institute of Cellular and Integrative Neurosciences (INCI) UMR7168/LC2 CNRS/ULP, Strasbourg, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Göritz
authors.forename: Renaud
authors.initials: R
authors.lastname: Thiebaut
authors.forename: Luc-Henri
authors.initials: LH
authors.lastname: Tessier
authors.forename: Katja
authors.initials: K
authors.lastname: Nieweg
authors.forename: Christoph
authors.initials: C
authors.lastname: Moehle
authors.forename: Isabelle
authors.initials: I
authors.lastname: Buard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dupont
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005372:Filipin; D005786:Gene Expression Regulation / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology; D000097568:Matrix Gla Protein
chemical_list: D000900:Anti-Bacterial Agents; D002135:Calcium-Binding Proteins; D002784:Cholesterol; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D005227:Fatty Acids; D005372:Filipin; D006419:Heme Oxygenase (Decyclizing); D012313:RNA; D000097568:Matrix Gla Protein; C491523:Hmox1 protein, rat