Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord

Detalhes bibliográficos
Autor(a) principal: Monteiro, Filipe A.
Data de Publicação: 2021
Outros Autores: Miranda, Rafael M., Samina, Marta C., Dias, Ana F., Raposo, Alexandre, Oliveira, Patrícia, Reguenga, Carlos, Castro, Diogo S., Lima, Deolinda
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47981
Resumo: © 2021 Monteiro, Miranda, Samina, Dias, Raposo, Oliveira, Reguenga, Castro and Lima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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spelling Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cordT-cell leukemia homeobox 3Chromatin immunoprecipitationDorsal hornExcitatory neuronSpinal cord© 2021 Monteiro, Miranda, Samina, Dias, Raposo, Oliveira, Reguenga, Castro and Lima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The spinal cord dorsal horn is a major station for integration and relay of somatosensory information and comprises both excitatory and inhibitory neuronal populations. The homeobox gene Tlx3 acts as a selector gene to control the development of late-born excitatory (dILB) neurons by specifying glutamatergic transmitter fate in dorsal spinal cord. However, since Tlx3 direct transcriptional targets remain largely unknown, it remains to be uncovered how Tlx3 functions to promote excitatory cell fate. Here we combined a genomics approach based on chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and expression profiling, with validation experiments in Tlx3 null embryos, to characterize the transcriptional program of Tlx3 in mouse embryonic dorsal spinal cord. We found most dILB neuron specific genes previously identified to be directly activated by Tlx3. Surprisingly, we found Tlx3 also directly represses many genes associated with the alternative inhibitory dILA neuronal fate. In both cases, direct targets include transcription factors and terminal differentiation genes, showing that Tlx3 directly controls cell identity at distinct levels. Our findings provide a molecular frame for the master regulatory role of Tlx3 in developing glutamatergic dILB neurons. In addition, they suggest a novel function for Tlx3 as direct repressor of GABAergic dILA identity, pointing to how generation of the two alternative cell fates being tightly coupled.This work is a result of the project Norte-01-0145-FEDER-000008 – Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work was also supported by FCT – Fundação para a Ciência e Tecnologia (Grants PTDC/SAU-OBD/099886/2008 to DL and PTDC/NEU-NMC/0315/2012 to DC) and Universidade do Porto/Banco Santander Totta (Projetos Pluridisciplinares to FM). We acknowledge the support of POCI-01-0145-FEDER-022122, granted to i3S Scientific Platform Advanced Light Microscopy, member of the national infrastructure PPBI-Portuguese Platform of BioImaging.FrontiersRepositório da Universidade de LisboaMonteiro, Filipe A.Miranda, Rafael M.Samina, Marta C.Dias, Ana F.Raposo, AlexandreOliveira, PatríciaReguenga, CarlosCastro, Diogo S.Lima, Deolinda2021-05-18T15:36:45Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47981engFront Cell Dev Biol. 2021 Apr 29;9:64269710.3389/fcell.2021.6426972296-634Xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:51:09Zoai:repositorio.ul.pt:10451/47981Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:55.552288Repositório 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 Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
title Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
spellingShingle Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
Monteiro, Filipe A.
T-cell leukemia homeobox 3
Chromatin immunoprecipitation
Dorsal horn
Excitatory neuron
Spinal cord
title_short Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
title_full Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
title_fullStr Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
title_full_unstemmed Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
title_sort Tlx3 exerts direct control in specifying excitatory over inhibitory neurons in the dorsal spinal cord
author Monteiro, Filipe A.
author_facet Monteiro, Filipe A.
Miranda, Rafael M.
Samina, Marta C.
Dias, Ana F.
Raposo, Alexandre
Oliveira, Patrícia
Reguenga, Carlos
Castro, Diogo S.
Lima, Deolinda
author_role author
author2 Miranda, Rafael M.
Samina, Marta C.
Dias, Ana F.
Raposo, Alexandre
Oliveira, Patrícia
Reguenga, Carlos
Castro, Diogo S.
Lima, Deolinda
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Monteiro, Filipe A.
Miranda, Rafael M.
Samina, Marta C.
Dias, Ana F.
Raposo, Alexandre
Oliveira, Patrícia
Reguenga, Carlos
Castro, Diogo S.
Lima, Deolinda
dc.subject.por.fl_str_mv T-cell leukemia homeobox 3
Chromatin immunoprecipitation
Dorsal horn
Excitatory neuron
Spinal cord
topic T-cell leukemia homeobox 3
Chromatin immunoprecipitation
Dorsal horn
Excitatory neuron
Spinal cord
description © 2021 Monteiro, Miranda, Samina, Dias, Raposo, Oliveira, Reguenga, Castro and Lima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2021
dc.date.none.fl_str_mv 2021-05-18T15:36:45Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/47981
url http://hdl.handle.net/10451/47981
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Cell Dev Biol. 2021 Apr 29;9:642697
10.3389/fcell.2021.642697
2296-634X
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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