DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex

Autores
Franz, Henriette; Villarreal, Alejandro; Heidrich, Stefanie; Videm, Pavankumar; Kilpert, Fabian; Mestres, Ivan; Calegari, Federico; Backofen, Rolf; Manke, Thomas; Vogel, Tanja
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatiooral activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telencephalon leads to cortical layering defects, indicating DOT1L activity and chromatin methylation at H3K79 impact on the cell cycle, and influence transcriptional programs conferring upper layer identity in early progenitors. Specifically, DOT1L prevents premature differentiation by increasing expression of genes that regulate asymmetric cell division (Vangl2, Cenpj). Loss of DOT1L results in reduced numbers of progenitors expressing genes including SoxB1 gene family members. Loss of DOT1L also leads to altered cortical distribution of deep layer neurons that express either TBR1, CTIP2 or SOX5, and less activation of transcriptional programs that are characteristic for upper layer neurons (Satb2, Pou3f3, Cux2, SoxC family members). Data from three different mouse models suggest that DOT1L balances transcriptional programs necessary for proper neuronal composition and distribution in the six cortical layers. Furthermore, because loss of DOT1L in the pre-neurogenic phase of development impairs specifically generation of SATB2-expressing upper layer neurons, our data suggest that DOT1L primes upper layer identity in cortical progenitors.
Fil: Franz, Henriette. Universität Freiburg Im Breisgau; Alemania
Fil: Villarreal, Alejandro. Universität Freiburg Im Breisgau; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Heidrich, Stefanie. Universität Freiburg Im Breisgau; Alemania
Fil: Videm, Pavankumar. Universität Freiburg Im Breisgau; Alemania
Fil: Kilpert, Fabian. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Mestres, Ivan. Technical University Dresden; Alemania
Fil: Calegari, Federico. Technical University Dresden; Alemania
Fil: Backofen, Rolf. Universidad de Copenhagen; Dinamarca. Universität Freiburg Im Breisgau; Alemania
Fil: Manke, Thomas. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Vogel, Tanja. Universität Freiburg Im Breisgau; Alemania
Materia
DOT1L
EPIGENETICS
NEURONAL LAYER SPECIFICATION
CORTICAL DEVELOPMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/88087
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/88087
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortexFranz, HenrietteVillarreal, AlejandroHeidrich, StefanieVidem, PavankumarKilpert, FabianMestres, IvanCalegari, FedericoBackofen, RolfManke, ThomasVogel, TanjaDOT1LEPIGENETICSNEURONAL LAYER SPECIFICATIONCORTICAL DEVELOPMENThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatiooral activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telencephalon leads to cortical layering defects, indicating DOT1L activity and chromatin methylation at H3K79 impact on the cell cycle, and influence transcriptional programs conferring upper layer identity in early progenitors. Specifically, DOT1L prevents premature differentiation by increasing expression of genes that regulate asymmetric cell division (Vangl2, Cenpj). Loss of DOT1L results in reduced numbers of progenitors expressing genes including SoxB1 gene family members. Loss of DOT1L also leads to altered cortical distribution of deep layer neurons that express either TBR1, CTIP2 or SOX5, and less activation of transcriptional programs that are characteristic for upper layer neurons (Satb2, Pou3f3, Cux2, SoxC family members). Data from three different mouse models suggest that DOT1L balances transcriptional programs necessary for proper neuronal composition and distribution in the six cortical layers. Furthermore, because loss of DOT1L in the pre-neurogenic phase of development impairs specifically generation of SATB2-expressing upper layer neurons, our data suggest that DOT1L primes upper layer identity in cortical progenitors.Fil: Franz, Henriette. Universität Freiburg Im Breisgau; AlemaniaFil: Villarreal, Alejandro. Universität Freiburg Im Breisgau; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Heidrich, Stefanie. Universität Freiburg Im Breisgau; AlemaniaFil: Videm, Pavankumar. Universität Freiburg Im Breisgau; AlemaniaFil: Kilpert, Fabian. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Mestres, Ivan. Technical University Dresden; AlemaniaFil: Calegari, Federico. Technical University Dresden; AlemaniaFil: Backofen, Rolf. Universidad de Copenhagen; Dinamarca. Universität Freiburg Im Breisgau; AlemaniaFil: Manke, Thomas. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Vogel, Tanja. Universität Freiburg Im Breisgau; AlemaniaOxford University Press2019-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88087Franz, Henriette; Villarreal, Alejandro; Heidrich, Stefanie; Videm, Pavankumar; Kilpert, Fabian; et al.; DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex; Oxford University Press; Nucleic Acids Research; 47; 1; 1-2019; 168-1830305-10481362-4962CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky953/5133670info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gky953info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:27:16Zoai:ri.conicet.gov.ar:11336/88087instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:27:16.386CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
title DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
spellingShingle DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
Franz, Henriette
DOT1L
EPIGENETICS
NEURONAL LAYER SPECIFICATION
CORTICAL DEVELOPMENT
title_short DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
title_full DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
title_fullStr DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
title_full_unstemmed DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
title_sort DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
dc.creator.none.fl_str_mv Franz, Henriette
Villarreal, Alejandro
Heidrich, Stefanie
Videm, Pavankumar
Kilpert, Fabian
Mestres, Ivan
Calegari, Federico
Backofen, Rolf
Manke, Thomas
Vogel, Tanja
author Franz, Henriette
author_facet Franz, Henriette
Villarreal, Alejandro
Heidrich, Stefanie
Videm, Pavankumar
Kilpert, Fabian
Mestres, Ivan
Calegari, Federico
Backofen, Rolf
Manke, Thomas
Vogel, Tanja
author_role author
author2 Villarreal, Alejandro
Heidrich, Stefanie
Videm, Pavankumar
Kilpert, Fabian
Mestres, Ivan
Calegari, Federico
Backofen, Rolf
Manke, Thomas
Vogel, Tanja
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DOT1L
EPIGENETICS
NEURONAL LAYER SPECIFICATION
CORTICAL DEVELOPMENT
topic DOT1L
EPIGENETICS
NEURONAL LAYER SPECIFICATION
CORTICAL DEVELOPMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatiooral activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telencephalon leads to cortical layering defects, indicating DOT1L activity and chromatin methylation at H3K79 impact on the cell cycle, and influence transcriptional programs conferring upper layer identity in early progenitors. Specifically, DOT1L prevents premature differentiation by increasing expression of genes that regulate asymmetric cell division (Vangl2, Cenpj). Loss of DOT1L results in reduced numbers of progenitors expressing genes including SoxB1 gene family members. Loss of DOT1L also leads to altered cortical distribution of deep layer neurons that express either TBR1, CTIP2 or SOX5, and less activation of transcriptional programs that are characteristic for upper layer neurons (Satb2, Pou3f3, Cux2, SoxC family members). Data from three different mouse models suggest that DOT1L balances transcriptional programs necessary for proper neuronal composition and distribution in the six cortical layers. Furthermore, because loss of DOT1L in the pre-neurogenic phase of development impairs specifically generation of SATB2-expressing upper layer neurons, our data suggest that DOT1L primes upper layer identity in cortical progenitors.
Fil: Franz, Henriette. Universität Freiburg Im Breisgau; Alemania
Fil: Villarreal, Alejandro. Universität Freiburg Im Breisgau; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Heidrich, Stefanie. Universität Freiburg Im Breisgau; Alemania
Fil: Videm, Pavankumar. Universität Freiburg Im Breisgau; Alemania
Fil: Kilpert, Fabian. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Mestres, Ivan. Technical University Dresden; Alemania
Fil: Calegari, Federico. Technical University Dresden; Alemania
Fil: Backofen, Rolf. Universidad de Copenhagen; Dinamarca. Universität Freiburg Im Breisgau; Alemania
Fil: Manke, Thomas. Max Planck Institute Of Immunobiology And Epigenetics; Alemania
Fil: Vogel, Tanja. Universität Freiburg Im Breisgau; Alemania
description Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatiooral activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telencephalon leads to cortical layering defects, indicating DOT1L activity and chromatin methylation at H3K79 impact on the cell cycle, and influence transcriptional programs conferring upper layer identity in early progenitors. Specifically, DOT1L prevents premature differentiation by increasing expression of genes that regulate asymmetric cell division (Vangl2, Cenpj). Loss of DOT1L results in reduced numbers of progenitors expressing genes including SoxB1 gene family members. Loss of DOT1L also leads to altered cortical distribution of deep layer neurons that express either TBR1, CTIP2 or SOX5, and less activation of transcriptional programs that are characteristic for upper layer neurons (Satb2, Pou3f3, Cux2, SoxC family members). Data from three different mouse models suggest that DOT1L balances transcriptional programs necessary for proper neuronal composition and distribution in the six cortical layers. Furthermore, because loss of DOT1L in the pre-neurogenic phase of development impairs specifically generation of SATB2-expressing upper layer neurons, our data suggest that DOT1L primes upper layer identity in cortical progenitors.
publishDate 2019
dc.date.none.fl_str_mv 2019-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/88087
Franz, Henriette; Villarreal, Alejandro; Heidrich, Stefanie; Videm, Pavankumar; Kilpert, Fabian; et al.; DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex; Oxford University Press; Nucleic Acids Research; 47; 1; 1-2019; 168-183
0305-1048
1362-4962
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88087
identifier_str_mv Franz, Henriette; Villarreal, Alejandro; Heidrich, Stefanie; Videm, Pavankumar; Kilpert, Fabian; et al.; DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex; Oxford University Press; Nucleic Acids Research; 47; 1; 1-2019; 168-183
0305-1048
1362-4962
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky953/5133670
info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gky953
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082726408486912
score 13.22299

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