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

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

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dc.contributor.author	Landeira, Bruna Soares
dc.contributor.author	Santana, Themis Taynah da Silva
dc.contributor.author	Araújo, Jéssica Alves de Medeiros
dc.contributor.author	Tabet, Elie I.
dc.contributor.author	Tannous, Bakhos A.
dc.contributor.author	Schroeder, Timm
dc.contributor.author	Costa, Marcos Romualdo
dc.date.accessioned	2017-01-16T13:04:57Z
dc.date.available	2017-01-16T13:04:57Z
dc.date.issued	2016-12
dc.description.resumo	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.	pt_BR
dc.identifier.uri	https://repositorio.ufrn.br/jspui/handle/123456789/21645
dc.language	eng	pt_BR
dc.rights	Acesso Aberto	pt_BR
dc.subject	Cortex	pt_BR
dc.subject	CREB signaling	pt_BR
dc.subject	Immature neurons	pt_BR
dc.subject	Dendritic differentiation	pt_BR
dc.subject	Neuronal survival	pt_BR
dc.title	Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development	pt_BR
dc.type	article	pt_BR