Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation

Detalhes bibliográficos
Autor(a) principal: Trigo, Guilherme Gomes
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/33029
Resumo: The human nervous system is composed of an intricate and complex neuronal network. Synapses are the building blocks of this network and so a correct formation of the pre- and postsynaptic terminal is necessary, which is driven by a dynamic organization of proteins in locu. Intra-axonal mRNA translation has been shown to provide the proteins necessary for axonal growth and pathfinding. However, it is still unclear how local protein synthesis regulates presynaptic formation. To address this question, we cultured rat embryonic hippocampal neurons in microfluidic chambers. These devices allow the physical and fluidic isolation of distal axons and, thus, allow the study of axonal intrinsic mechanisms. We found that intra-axonal mRNA translation is required for presynaptic differentiation. We further observed that presynaptic differentiation induced by fibroblast growth factor 22 and Poly-D-Lysine-coated beads is accompanied by an increase of translational markers in newly formed presynaptic sites. Together, these results demonstrate the existence of local intra-axonal mRNA translation during synapse formation.
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spelling Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formationLocal mRNA translationAxonsPresynaptic differentiationFGF22The human nervous system is composed of an intricate and complex neuronal network. Synapses are the building blocks of this network and so a correct formation of the pre- and postsynaptic terminal is necessary, which is driven by a dynamic organization of proteins in locu. Intra-axonal mRNA translation has been shown to provide the proteins necessary for axonal growth and pathfinding. However, it is still unclear how local protein synthesis regulates presynaptic formation. To address this question, we cultured rat embryonic hippocampal neurons in microfluidic chambers. These devices allow the physical and fluidic isolation of distal axons and, thus, allow the study of axonal intrinsic mechanisms. We found that intra-axonal mRNA translation is required for presynaptic differentiation. We further observed that presynaptic differentiation induced by fibroblast growth factor 22 and Poly-D-Lysine-coated beads is accompanied by an increase of translational markers in newly formed presynaptic sites. Together, these results demonstrate the existence of local intra-axonal mRNA translation during synapse formation.O sistema nervoso humano é composto por uma rede neuronal intricada e complexa. As sinapses constituem a base da rede neuronal e, portanto, é necessária uma formação correta do terminal pré e pós-sináptico, que é impulsionado por uma organização dinâmica de proteínas in locu. Foi demonstrado que a tradução intra-axonal do mRNA fornece as proteínas necessárias para o crescimento axonal e o pathfinding. No entanto, ainda não está claro qual o papel da síntese local de proteínas na formação pré-sináptica. Com o intuito de responder a esta questão, foram plaqueados em câmaras microfluídicas neurónios embrionários do hipocampo de rato. Estes dispositivos permitem o isolamento físico e fluídico dos axónios distais e, assim, permitem o estudo dos mecanismos intrínsecos dos axónios. Descobrimos que a tradução intra-axonal do mRNA é necessária para a diferenciação pré-sináptica. Observamos ainda que a diferenciação pré-sináptica induzida pelo fator de crescimento de fibroblastos 22 e Beads revestidas com Poli-D-Lisina é acompanhada por um aumento de marcadores de tradução em locais pré-sinápticos recém-formados. Estes resultados demonstram a existência de tradução de mRNA intra-axonal local durante a formação de sinapses.2023-12-20T00:00:00Z2021-12-13T00:00:00Z2021-12-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/33029engTrigo, Guilherme Gomesinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:03:32Zoai:ria.ua.pt:10773/33029Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:04:32.382241Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
title Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
spellingShingle Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
Trigo, Guilherme Gomes
Local mRNA translation
Axons
Presynaptic differentiation
FGF22
title_short Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
title_full Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
title_fullStr Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
title_full_unstemmed Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
title_sort Determine if intra-axonal mRNA translation occurs at discrete “hot spots” during synapse formation
author Trigo, Guilherme Gomes
author_facet Trigo, Guilherme Gomes
author_role author
dc.contributor.author.fl_str_mv Trigo, Guilherme Gomes
dc.subject.por.fl_str_mv Local mRNA translation
Axons
Presynaptic differentiation
FGF22
topic Local mRNA translation
Axons
Presynaptic differentiation
FGF22
description The human nervous system is composed of an intricate and complex neuronal network. Synapses are the building blocks of this network and so a correct formation of the pre- and postsynaptic terminal is necessary, which is driven by a dynamic organization of proteins in locu. Intra-axonal mRNA translation has been shown to provide the proteins necessary for axonal growth and pathfinding. However, it is still unclear how local protein synthesis regulates presynaptic formation. To address this question, we cultured rat embryonic hippocampal neurons in microfluidic chambers. These devices allow the physical and fluidic isolation of distal axons and, thus, allow the study of axonal intrinsic mechanisms. We found that intra-axonal mRNA translation is required for presynaptic differentiation. We further observed that presynaptic differentiation induced by fibroblast growth factor 22 and Poly-D-Lysine-coated beads is accompanied by an increase of translational markers in newly formed presynaptic sites. Together, these results demonstrate the existence of local intra-axonal mRNA translation during synapse formation.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-13T00:00:00Z
2021-12-13
2023-12-20T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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