A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord

Detalhes bibliográficos
Autor(a) principal: Borromeo, M. D.
Data de Publicação: 2014
Outros Autores: Meredith, D. M., Castro, D. S., Chang, J. C., Tung, K.-C., Guillemot, F., Johnson, J. E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.7/523
Resumo: The proper balance of excitatory and inhibitory neurons is crucial for normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have contrasting functions in specifying these neurons. To understand how Ascl1 and Ptf1a function in this process, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly regulates genes with roles in several steps of the neurogenic program, including Notch signaling, neuronal differentiation, axon guidance and synapse formation. By contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Ascl1 and Ptf1a bind sequences primarily enriched for a specific E-Box motif (CAGCTG) and for secondary motifs used by Sox, Rfx, Pou and homeodomain factors. Ptf1a also binds sequences uniquely enriched in the CAGATG E-box and in the binding motif for its co-factor Rbpj, providing two factors that influence the specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding of how these DNA-binding proteins function in neuronal development, particularly as key regulators of homeodomain TFs required for neuronal subtype specification.
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spelling A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cordChIP-SeqbHLH transcription factorDorsal neural tubeNeuronal subtype specificationMouseChickAscl1Ptf1aThe proper balance of excitatory and inhibitory neurons is crucial for normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have contrasting functions in specifying these neurons. To understand how Ascl1 and Ptf1a function in this process, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly regulates genes with roles in several steps of the neurogenic program, including Notch signaling, neuronal differentiation, axon guidance and synapse formation. By contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Ascl1 and Ptf1a bind sequences primarily enriched for a specific E-Box motif (CAGCTG) and for secondary motifs used by Sox, Rfx, Pou and homeodomain factors. Ptf1a also binds sequences uniquely enriched in the CAGATG E-box and in the binding motif for its co-factor Rbpj, providing two factors that influence the specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding of how these DNA-binding proteins function in neuronal development, particularly as key regulators of homeodomain TFs required for neuronal subtype specification.National Institutes of Health grants: ([F31NS705592, R01 HD037932, R01 NS032817, F31 NS061440Company of BiologistsARCABorromeo, M. D.Meredith, D. M.Castro, D. S.Chang, J. C.Tung, K.-C.Guillemot, F.Johnson, J. E.2015-11-24T16:34:48Z2014-06-122014-06-12T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/523engA transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord Mark D. Borromeo, David M. Meredith, Diogo S. Castro, Joshua C. Chang, Kuang-Chi Tung, Francois Guillemot, Jane E. Johnson Development 2014 141: 2803-2812; doi: 10.1242/dev.10586610.1242/dev.105866info: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:RCAAP2022-11-29T14:34:53Zoai:arca.igc.gulbenkian.pt:10400.7/523Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:46.732758Repositório 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 A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
title A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
spellingShingle A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
Borromeo, M. D.
ChIP-Seq
bHLH transcription factor
Dorsal neural tube
Neuronal subtype specification
Mouse
Chick
Ascl1
Ptf1a
title_short A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
title_full A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
title_fullStr A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
title_full_unstemmed A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
title_sort A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
author Borromeo, M. D.
author_facet Borromeo, M. D.
Meredith, D. M.
Castro, D. S.
Chang, J. C.
Tung, K.-C.
Guillemot, F.
Johnson, J. E.
author_role author
author2 Meredith, D. M.
Castro, D. S.
Chang, J. C.
Tung, K.-C.
Guillemot, F.
Johnson, J. E.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv ARCA
dc.contributor.author.fl_str_mv Borromeo, M. D.
Meredith, D. M.
Castro, D. S.
Chang, J. C.
Tung, K.-C.
Guillemot, F.
Johnson, J. E.
dc.subject.por.fl_str_mv ChIP-Seq
bHLH transcription factor
Dorsal neural tube
Neuronal subtype specification
Mouse
Chick
Ascl1
Ptf1a
topic ChIP-Seq
bHLH transcription factor
Dorsal neural tube
Neuronal subtype specification
Mouse
Chick
Ascl1
Ptf1a
description The proper balance of excitatory and inhibitory neurons is crucial for normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have contrasting functions in specifying these neurons. To understand how Ascl1 and Ptf1a function in this process, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly regulates genes with roles in several steps of the neurogenic program, including Notch signaling, neuronal differentiation, axon guidance and synapse formation. By contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Ascl1 and Ptf1a bind sequences primarily enriched for a specific E-Box motif (CAGCTG) and for secondary motifs used by Sox, Rfx, Pou and homeodomain factors. Ptf1a also binds sequences uniquely enriched in the CAGATG E-box and in the binding motif for its co-factor Rbpj, providing two factors that influence the specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding of how these DNA-binding proteins function in neuronal development, particularly as key regulators of homeodomain TFs required for neuronal subtype specification.
publishDate 2014
dc.date.none.fl_str_mv 2014-06-12
2014-06-12T00:00:00Z
2015-11-24T16:34:48Z
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/10400.7/523
url http://hdl.handle.net/10400.7/523
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord Mark D. Borromeo, David M. Meredith, Diogo S. Castro, Joshua C. Chang, Kuang-Chi Tung, Francois Guillemot, Jane E. Johnson Development 2014 141: 2803-2812; doi: 10.1242/dev.105866
10.1242/dev.105866
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 Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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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