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Transient CREB-mediated transcription is key in direct neuronal reprogramming.

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.

SUBMITTER: Gascon S

PROVIDER: S-EPMC5345748 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Transient CREB-mediated transcription is key in direct neuronal reprogramming.

Gascón Sergio S Ortega Felipe F Götz Magdalena M

Neurogenesis (Austin, Tex.) 20170206 1

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 mediate ...[more]

PMID: 28321434

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