Repressor element-1 silencing transcription/neuron-restrictive silencer factor is required for neural sodium channel expression during development of Xenopus

Armisen, R; Fuentes R.; Olguin, P.; Cabrejos, ME; Kukuljan M.

Abstract

The ability of neurons to fire rapid action potential relies on the expression of voltage-gated sodium channels; the onset of the transcription of genes that encode these channels occurs during early neuronal development. The factors that direct and regulate the specific expression of ion channels are not well understood. Repressor element-1 silencing transcription/ neuron-restrictive silencer factor (REST/NRSF) is a transcriptional regulator characterized as a repressor of the expression of NaV1.2, the gene encoding the voltage-gated sodium channel most abundantly expressed in the CNS, as well as of the expression of numerous other neuronal genes. In mammals, REST/NRSF is expressed mostly in non-neural cell types and immature neurons, and it is downregulated on neural maturation. To understand the mechanisms that govern sodium channel gene transcription and to explore the role of REST/NRSF in vivo, we inhibited REST/NRSF action in developing Xenopus laevis embryos by means of a dominant negative protein or antisense oligonucleotides. Contrary to what was expected, these maneuvers result in the decrease of the expression of the NaV1.2 gene, as well as of other neuronal genes in the primary spinal neurons and cranial ganglia, without overt perturbation of neurogenesis. These results, together with the demonstration of robust REST/NRSF expression in primary spinal neurons, suggest that REST/NRSF is required for the acquisition of the differentiated functional neuronal phenotype during early development. Furthermore, they suggest that REST/NRSF may be used to activate or repress transcription of neuronal genes in distinct cellular and developmental contexts.

Más información

Título según WOS: Repressor element-1 silencing transcription/neuron-restrictive silencer factor is required for neural sodium channel expression during development of Xenopus
Título según SCOPUS: Repressor element-1 silencing transcription/neuron-restrictive silencer factor is required for neural sodium channel expression during development of Xenopus
Título de la Revista: JOURNAL OF NEUROSCIENCE
Volumen: 22
Número: 19
Editorial: SOC NEUROSCIENCE
Fecha de publicación: 2002
Página de inicio: 8347
Página final: 8351
Idioma: English
Notas: ISI, SCOPUS