Response of Schwann cells to action potentials in development.
Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes. We report that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through P2 receptors on SCs and intracellular signaling pathways involving Ca2+, Ca2+/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3',5'-monophosphate response element binding protein, and expression of c-fos and Krox-24. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals.
Stevens
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Laboratory of Developmental Neurobiology, National Institutes of Health, National Institute of Child Health and Human Development, Building 49, Room 5A38, 49 Convent Drive, Bethesda, MD 20892, USA.
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D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D016762:Genes, fos; D017874:Immediate-Early Proteins; D051379:Mice; D018613:Microscopy, Confocal; D009186:Myelin Sheath / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D018048:Receptors, Purinergic P2; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium