The Etv1 transcription factor activity-dependently downregulates a set of genes controlling cell growth and differentiation in maturing cerebellar granule cells

• Published in: Biochemical and biophysical research communications Vol. 473; no. 4; pp. 1071 - 1077
• Main Authors: Okazawa, Makoto, Abe, Haruka, Nakanishi, Shigetada
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.05.2016
• Subjects: Activity-dependent regulation; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cell culture; Cell Differentiation - physiology; Cell Proliferation - physiology; Cells, Cultured; Cerebellum; Cerebellum - cytology; Cerebellum - physiology; DNA-Binding Proteins - metabolism; Down-Regulation - physiology; Etv1; Gene Expression Regulation, Developmental - physiology; Mice; Mice, Inbred ICR; Neurogenesis - physiology; Neurons - cytology; Neurons - physiology; Synaptic maturation; Transcription Factors - metabolism; Transcriptional regulation; Cerebellum; Cell culture; Synaptic maturation; CPP; AMPA; Activity-dependent regulation; Etv1; Transcriptional regulation; CsA; CaN; CaMKII; NMDA; NBQX
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.04.017

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 Ca2+/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. •Immaturation genes of granule cells are downregulated in an activity-dependent manner during cerebellar maturation.•The downregulation of immaturation genes is controlled by a unified sequential CaMKII-mediated signaling cascade.•Etv1 is the primary transcription factor that directs the downregulation of immaturation genes.