Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning

Autores
Abad, Clemer; Robayo, Maria C.; Muñiz Moreno, Maria del Mar; Bernardi, Maria Trinidad; Otero, Maria G.; Kosanovic, Christina; Griswold, Anthony J.; Pierson, Tyler Mark; Walz, Katherina; Young, Juan
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
GATAD2B (GATA zinc finger domain containing 2B) variants are associated with the neurodevelopmental syndrome GAND, characterized by intellectual disability (ID), infantile hypotonia, apraxia of speech, epilepsy, macrocephaly and distinct facial features. GATAD2B encodes for a subunit of the Nucleosome Remodeling and Histone Deacetylase (NuRD) complex. NuRD controls transcriptional programs critical for proper neurodevelopment by coupling histone deacetylase with ATP-dependent chromatin remodeling activity. To study mechanisms of pathogenesis for GAND, we characterized a mouse model harboring an inactivating mutation in Gatad2b. Homozygous Gatad2b mutants die perinatally, while haploinsufficient Gatad2b mice exhibit behavioral abnormalities resembling the clinical features of GAND patients. We also observed abnormal cortical patterning, and cellular proportions and cell-specific alterations in the developmental transcriptome in these mice. scRNAseq of embryonic cortex indicated misexpression of genes key for corticogenesis and associated with neurodevelopmental syndromes such as Bcl11b, Nfia and H3f3b and Sox5. These data suggest a crucial role for Gatad2b in brain development.
Fil: Abad, Clemer. University of Miami; Estados Unidos
Fil: Robayo, Maria C.. University of Miami; Estados Unidos
Fil: Muñiz Moreno, Maria del Mar. University of Miami; Estados Unidos
Fil: Bernardi, Maria Trinidad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Otero, Maria G.. University of Miami; Estados Unidos
Fil: Kosanovic, Christina. University of Miami; Estados Unidos
Fil: Griswold, Anthony J.. University of Miami; Estados Unidos
Fil: Pierson, Tyler Mark. University of Miami; Estados Unidos
Fil: Walz, Katherina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Young, Juan. University of Miami; Estados Unidos
Materia
Gatad2b
GAND
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/276359
Acceder
id CONICETDig_bef29ccd83bc28d002357309f6ae9152
oai_identifier_str oai:ri.conicet.gov.ar:11336/276359
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterningAbad, ClemerRobayo, Maria C.Muñiz Moreno, Maria del MarBernardi, Maria TrinidadOtero, Maria G.Kosanovic, ChristinaGriswold, Anthony J.Pierson, Tyler MarkWalz, KatherinaYoung, JuanGatad2bGANDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1GATAD2B (GATA zinc finger domain containing 2B) variants are associated with the neurodevelopmental syndrome GAND, characterized by intellectual disability (ID), infantile hypotonia, apraxia of speech, epilepsy, macrocephaly and distinct facial features. GATAD2B encodes for a subunit of the Nucleosome Remodeling and Histone Deacetylase (NuRD) complex. NuRD controls transcriptional programs critical for proper neurodevelopment by coupling histone deacetylase with ATP-dependent chromatin remodeling activity. To study mechanisms of pathogenesis for GAND, we characterized a mouse model harboring an inactivating mutation in Gatad2b. Homozygous Gatad2b mutants die perinatally, while haploinsufficient Gatad2b mice exhibit behavioral abnormalities resembling the clinical features of GAND patients. We also observed abnormal cortical patterning, and cellular proportions and cell-specific alterations in the developmental transcriptome in these mice. scRNAseq of embryonic cortex indicated misexpression of genes key for corticogenesis and associated with neurodevelopmental syndromes such as Bcl11b, Nfia and H3f3b and Sox5. These data suggest a crucial role for Gatad2b in brain development.Fil: Abad, Clemer. University of Miami; Estados UnidosFil: Robayo, Maria C.. University of Miami; Estados UnidosFil: Muñiz Moreno, Maria del Mar. University of Miami; Estados UnidosFil: Bernardi, Maria Trinidad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Otero, Maria G.. University of Miami; Estados UnidosFil: Kosanovic, Christina. University of Miami; Estados UnidosFil: Griswold, Anthony J.. University of Miami; Estados UnidosFil: Pierson, Tyler Mark. University of Miami; Estados UnidosFil: Walz, Katherina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Young, Juan. University of Miami; Estados UnidosNature Publishing Group2024-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/276359Abad, Clemer; Robayo, Maria C.; Muñiz Moreno, Maria del Mar; Bernardi, Maria Trinidad; Otero, Maria G.; et al.; Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning; Nature Publishing Group; Translational Psychiatry; 14; 1; 1-2024; 1-132158-3188CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41398-023-02678-xinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41398-023-02678-xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:50:03Zoai:ri.conicet.gov.ar:11336/276359instacron: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:34982026-08-25 14:50:03.499CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
title Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
spellingShingle Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
Abad, Clemer
Gatad2b
GAND
title_short Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
title_full Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
title_fullStr Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
title_full_unstemmed Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
title_sort Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
dc.creator.none.fl_str_mv Abad, Clemer
Robayo, Maria C.
Muñiz Moreno, Maria del Mar
Bernardi, Maria Trinidad
Otero, Maria G.
Kosanovic, Christina
Griswold, Anthony J.
Pierson, Tyler Mark
Walz, Katherina
Young, Juan
author Abad, Clemer
author_facet Abad, Clemer
Robayo, Maria C.
Muñiz Moreno, Maria del Mar
Bernardi, Maria Trinidad
Otero, Maria G.
Kosanovic, Christina
Griswold, Anthony J.
Pierson, Tyler Mark
Walz, Katherina
Young, Juan
author_role author
author2 Robayo, Maria C.
Muñiz Moreno, Maria del Mar
Bernardi, Maria Trinidad
Otero, Maria G.
Kosanovic, Christina
Griswold, Anthony J.
Pierson, Tyler Mark
Walz, Katherina
Young, Juan
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Gatad2b
GAND
topic Gatad2b
GAND
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv GATAD2B (GATA zinc finger domain containing 2B) variants are associated with the neurodevelopmental syndrome GAND, characterized by intellectual disability (ID), infantile hypotonia, apraxia of speech, epilepsy, macrocephaly and distinct facial features. GATAD2B encodes for a subunit of the Nucleosome Remodeling and Histone Deacetylase (NuRD) complex. NuRD controls transcriptional programs critical for proper neurodevelopment by coupling histone deacetylase with ATP-dependent chromatin remodeling activity. To study mechanisms of pathogenesis for GAND, we characterized a mouse model harboring an inactivating mutation in Gatad2b. Homozygous Gatad2b mutants die perinatally, while haploinsufficient Gatad2b mice exhibit behavioral abnormalities resembling the clinical features of GAND patients. We also observed abnormal cortical patterning, and cellular proportions and cell-specific alterations in the developmental transcriptome in these mice. scRNAseq of embryonic cortex indicated misexpression of genes key for corticogenesis and associated with neurodevelopmental syndromes such as Bcl11b, Nfia and H3f3b and Sox5. These data suggest a crucial role for Gatad2b in brain development.
Fil: Abad, Clemer. University of Miami; Estados Unidos
Fil: Robayo, Maria C.. University of Miami; Estados Unidos
Fil: Muñiz Moreno, Maria del Mar. University of Miami; Estados Unidos
Fil: Bernardi, Maria Trinidad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Otero, Maria G.. University of Miami; Estados Unidos
Fil: Kosanovic, Christina. University of Miami; Estados Unidos
Fil: Griswold, Anthony J.. University of Miami; Estados Unidos
Fil: Pierson, Tyler Mark. University of Miami; Estados Unidos
Fil: Walz, Katherina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Young, Juan. University of Miami; Estados Unidos
description GATAD2B (GATA zinc finger domain containing 2B) variants are associated with the neurodevelopmental syndrome GAND, characterized by intellectual disability (ID), infantile hypotonia, apraxia of speech, epilepsy, macrocephaly and distinct facial features. GATAD2B encodes for a subunit of the Nucleosome Remodeling and Histone Deacetylase (NuRD) complex. NuRD controls transcriptional programs critical for proper neurodevelopment by coupling histone deacetylase with ATP-dependent chromatin remodeling activity. To study mechanisms of pathogenesis for GAND, we characterized a mouse model harboring an inactivating mutation in Gatad2b. Homozygous Gatad2b mutants die perinatally, while haploinsufficient Gatad2b mice exhibit behavioral abnormalities resembling the clinical features of GAND patients. We also observed abnormal cortical patterning, and cellular proportions and cell-specific alterations in the developmental transcriptome in these mice. scRNAseq of embryonic cortex indicated misexpression of genes key for corticogenesis and associated with neurodevelopmental syndromes such as Bcl11b, Nfia and H3f3b and Sox5. These data suggest a crucial role for Gatad2b in brain development.
publishDate 2024
dc.date.none.fl_str_mv 2024-01
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/11336/276359
Abad, Clemer; Robayo, Maria C.; Muñiz Moreno, Maria del Mar; Bernardi, Maria Trinidad; Otero, Maria G.; et al.; Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning; Nature Publishing Group; Translational Psychiatry; 14; 1; 1-2024; 1-13
2158-3188
CONICET Digital
CONICET
url http://hdl.handle.net/11336/276359
identifier_str_mv Abad, Clemer; Robayo, Maria C.; Muñiz Moreno, Maria del Mar; Bernardi, Maria Trinidad; Otero, Maria G.; et al.; Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning; Nature Publishing Group; Translational Psychiatry; 14; 1; 1-2024; 1-13
2158-3188
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://www.nature.com/articles/s41398-023-02678-x
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41398-023-02678-x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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_ 1874774745782681600
score 13.365483

Publicaciones similares