title: The Etv1 transcription factor activity-dependently downregulates a set of genes controlling cell growth and differentiation in maturing cerebellar granule cells.
abstract: In the early postnatal period, cerebellar granule cells exhibit an activity-dependent downregulation of a set of immaturation genes involved in cell growth and migration and are shifted to establishment of a mature network formation. Through the use of a granule cell culture and both pharmacological and RNA interference (siRNA) analyses, the present investigation revealed that the downregulation of these immaturation genes is controlled by strikingly unified signaling mechanisms that operate sequentially through the stimulation of AMPA and NMDA receptors, tetrodotoxin-sensitive Na(+) channels and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). This signaling cascade induces the Etv1 transcription factor, and knockdown of Etv1 by a siRNA technique prevented this activity-dependent downregulation of immaturation genes. Thus, taken into consideration the mechanism that controls the upregulation of maturation genes involved in synaptic formation, these results indicate that Etv1 orchestrates the activity-dependent regulation of both maturation and immaturation genes in developing granule cells and plays a key role in specifying the identity of mature granule cells in the cerebellum.
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan; Department of Vascular Physiology, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan. Electronic address: okazawa@ncvc.go.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Okazawa
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
authors.forename: Shigetada
authors.initials: S
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C490641:Etv1 protein, mouse; D014157:Transcription Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Activity-dependent regulation; Cell culture; Cerebellum; Etv1; Synaptic maturation; Transcriptional regulation