Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development

Neuronal survival and morphological maturation depends on the action of the transcription factor calcium responsive element binding protein (CREB), which regulates expression of several target genes in an activity-dependent manner. However, it remains largely unknown whether CREB-mediated transcript...

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Principais autores: Landeira, Bruna Soares, Santana, Themis Taynah da Silva, Araújo, Jéssica Alves de Medeiros, Tabet, Elie I., Tannous, Bakhos A., Schroeder, Timm, Costa, Marcos Romualdo
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Idioma:eng
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Cortex
CREB signaling
Immature neurons
Dendritic differentiation
Neuronal survival
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/21645
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spelling ri-123456789-216452021-07-09T20:41:59Z Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development Landeira, Bruna Soares Santana, Themis Taynah da Silva Araújo, Jéssica Alves de Medeiros Tabet, Elie I. Tannous, Bakhos A. Schroeder, Timm Costa, Marcos Romualdo Cortex CREB signaling Immature neurons Dendritic differentiation Neuronal survival Neuronal survival and morphological maturation depends on the action of the transcription factor calcium responsive element binding protein (CREB), which regulates expression of several target genes in an activity-dependent manner. However, it remains largely unknown whether CREB-mediated transcription could play a role at early stages of neuronal differentiation, prior to the establishment of functional synaptic contacts. Here, we show that CREB is phosphorylated at very early stages of neuronal differentiation in vivo and in vitro, even in the absence of depolarizing agents. Using genetic tools, we also show that inhibition of CREB-signaling affects neuronal growth and survival in vitro without affecting cell proliferation and neurogenesis. Expression of A-CREB or M-CREB, 2 dominant-negative inhibitors of CREB, decreases cell survival and the complexity of neuronal arborization. Similar changes are observed in neurons treated with protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitors, which also show decreased levels of pCREBSer133. Notably, expression of CREB-FY, a Tyr134Phe CREB mutant with a lower Km for phosphorylation, partly rescues the effects of PKA and CaMKII inhibition. Our data indicate that CREB-mediated signaling play important roles at early stages of cortical neuron differentiation, prior to the establishment of fully functional synaptic contacts. 2017-01-16T13:04:57Z 2017-01-16T13:04:57Z 2016-12 article https://repositorio.ufrn.br/jspui/handle/123456789/21645 eng Acesso Aberto application/pdf
institution Repositório Institucional
collection RI - UFRN
language eng
topic Cortex
CREB signaling
Immature neurons
Dendritic differentiation
Neuronal survival
spellingShingle Cortex
CREB signaling
Immature neurons
Dendritic differentiation
Neuronal survival
Landeira, Bruna Soares
Santana, Themis Taynah da Silva
Araújo, Jéssica Alves de Medeiros
Tabet, Elie I.
Tannous, Bakhos A.
Schroeder, Timm
Costa, Marcos Romualdo
Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
description Neuronal survival and morphological maturation depends on the action of the transcription factor calcium responsive element binding protein (CREB), which regulates expression of several target genes in an activity-dependent manner. However, it remains largely unknown whether CREB-mediated transcription could play a role at early stages of neuronal differentiation, prior to the establishment of functional synaptic contacts. Here, we show that CREB is phosphorylated at very early stages of neuronal differentiation in vivo and in vitro, even in the absence of depolarizing agents. Using genetic tools, we also show that inhibition of CREB-signaling affects neuronal growth and survival in vitro without affecting cell proliferation and neurogenesis. Expression of A-CREB or M-CREB, 2 dominant-negative inhibitors of CREB, decreases cell survival and the complexity of neuronal arborization. Similar changes are observed in neurons treated with protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitors, which also show decreased levels of pCREBSer133. Notably, expression of CREB-FY, a Tyr134Phe CREB mutant with a lower Km for phosphorylation, partly rescues the effects of PKA and CaMKII inhibition. Our data indicate that CREB-mediated signaling play important roles at early stages of cortical neuron differentiation, prior to the establishment of fully functional synaptic contacts.
format article
author Landeira, Bruna Soares
Santana, Themis Taynah da Silva
Araújo, Jéssica Alves de Medeiros
Tabet, Elie I.
Tannous, Bakhos A.
Schroeder, Timm
Costa, Marcos Romualdo
author_facet Landeira, Bruna Soares
Santana, Themis Taynah da Silva
Araújo, Jéssica Alves de Medeiros
Tabet, Elie I.
Tannous, Bakhos A.
Schroeder, Timm
Costa, Marcos Romualdo
author_sort Landeira, Bruna Soares
title Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
title_short Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
title_full Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
title_fullStr Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
title_full_unstemmed Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
title_sort activity-independent effects of creb on neuronal survival and differentiation during mouse cerebral cortex development
publishDate 2017
url https://repositorio.ufrn.br/jspui/handle/123456789/21645
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