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Transient CREB-mediated transcription is key in direct neuronal reprogramming

Neurogenesis (Austin). 2017 Feb 6;4(1):e1285383. doi: 10.1080/23262133.2017.1285383. eCollection 2017.

Authors/Editors: Gascón S, Ortega F, Götz M.
Publication Date: 2017

2017_02_gascon

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.

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