Glia-induced neuronal differentiation by transcriptional regulation.
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.
Göritz
Christian
C
Department of Neurotransmission/Neuroendocrine Secretion, Institute of Cellular and Integrative Neurosciences (INCI) UMR7168/LC2 CNRS/ULP, Strasbourg, France.
Thiebaut
Renaud
R
Tessier
Luc-Henri
LH
Nieweg
Katja
K
Moehle
Christoph
C
Buard
Isabelle
I
Dupont
Jean-Luc
JL
Schurgers
Leon J
LJ
Schmitz
Gerd
G
Pfrieger
Frank W
FW
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
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