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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/88087
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:38:07Zoai: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:34982025-09-29 09:38:07.767CONICET 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 |
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1844613204525711360 |
score |
13.070432 |