Transient CREB-mediated transcription is key in direct neuronal reprogramming. Issue 1 (1st January 2017)

• Record Type: Journal Article
• Authors: Gascón, Sergio; Ortega, Felipe; Götz, Magdalena
• Is Part Of: Neurogenesis. Volume 4:Issue 1(2017)
• Publication Date: 2017-01-01
• Subjects: Bcl-2 -- CREB -- direct reprogramming -- Forskolin -- ICER -- immediate early genes -- neurogenesis; Neurogenesis -- Periodicals; Periodicals; 612.64018
• DOI: 10.1080/23262133.2017.1285383
• Languages: English
• ISSNs: 2326-2133

Abstract

ABSTRACT: Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming – including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1. Contrarily, persistent over-activation by CREB-VP16 or persistent inhibition by ICER interferes with neuronal reprogramming, with the latter enhancing cell death. Taken together our work shows transient CREB activation as a key effector in neuronal reprogramming.