RT Journal Article
T1 CBP and SRF co-regulate dendritic growth and synaptic maturation.
A1 Del Blanco, Beatriz
A1 Guiretti, Deisy
A1 Tomasoni, Romana
A1 Lopez-Cascales, María T
A1 Muñoz-Viana, Rafael
A1 Lipinski, Michal
A1 Scandaglia, Marilyn
A1 Coca, Yaiza
A1 Olivares, Roman
A1 Valor, Luis M
A1 Herrera, Eloisa
A1 Barco, Angel
K1 Neuroscience
K1 Neurological disorders
AB The CREB-binding protein (CBP) exerts tight control of developmental processes. Here, we investigated the consequences of its selective ablation in newborn neurons. Mice in which CBP was eliminated during neuronal differentiation showed perinatal death and defective diaphragm innervation. Adult-born neurons also showed impaired growth and maturation after inducible and restricted CBP loss in dentate gyrus neuroprogenitors. Consistent with these in vivo findings, cultured neurons displayed impaired outgrowth, immature spines, and deficient activity-dependent synaptic remodeling after CBP ablation. These deficits coincided with broad transcriptional changes affecting genes involved in neuronal growth and plasticity. The affected gene set included many predicted targets of both CBP and the serum response factor (SRF), an activity-regulated transcription factor involved in structural plasticity. Notably, increasing SRF activity in a CBP-independent manner ameliorated the transcriptional, synaptic, and growth defects. These results underscore the relevance of CBP-SRF interactions during neuronal outgrowth and synaptic maturation, and demonstrate that CBP plays an essential role in supporting the gene program underlying the last steps of neuronal differentiation, both during development and in the adult brain.
PB Nature Publishing Group
YR 2019
FD 2019-03-08
LK http://hdl.handle.net/10668/13681
UL http://hdl.handle.net/10668/13681
LA en
NO Del Blanco B, Guiretti D, Tomasoni R, Lopez-Cascales MT, Muñoz-Viana R, Lipinski M, et al. CBP and SRF co-regulate dendritic growth and synaptic maturation. Cell Death Differ. 2019 Nov;26(11):2208-2222.
NO BdB is the recipient of a “Juan de La Cierva” contract from the Spanish Ministry of Economy and Competitiveness (MINECO). MTL-C is supported by a contract (BES-2017-081298) from Spanish Ministry of Economy and Competitiveness (MINECO). This research was supported by grants SAF2017-87928-R, BFU2016-77605-P, PCIN-2015-192-C02-01 and PCIN-2015-192-C02-02 (both grants are part of the ERA-NET NEURON JTC2015 project ChromISyn), and SEV-2017-0723 from MINECO co-financed by ERDF, grant PROMETEO/2016/026 from the Generalitat Valenciana, grant RGP0039/2017 from the Human Frontiers Science Program Organization (HFSPO), and a grant from the Alicia Koplowitz Foundation. The Instituto de Neurociencias is a “Centre of Excellence Severo Ochoa”.
DS RISalud
RD Apr 4, 2025