X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain

Autores
Cabrera Zapata, L. E.; Arevalo, M. A.; Garcia-Segura, L. M.; Cambiasso, M. J.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cabrera Zapata, Lucas Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.
Fil: Arévalo, María Ángeles. Instituto Cajal; España.
Fil: Arévalo, María Ángeles. Instituto de Salud Carlos III; España.
Fil: Garcia-Segura, Luis Miguel. Instituto Cajal; España.
Fil: Garcia-Segura, Luis Miguel. Instituto de Salud Carlos III; España.
Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.
Several X-linked genes are involved in neuronal growth and differentiation and may contribute to the generation of sex differences in brain. Previous results showed that XX hypothalamic neurons grow at a faster rate of development and exhibit higher expression of the neuritogenic gen neurogenin 3 (Ngn3) than XY neurons, independently of gonadal hormones. Since Ngn3 is an autosomal gene, such sex differences should be consequence of differences in the expression of X or Y chromosome genes. Using the Four Core Genotypes mouse model, we analyzed the expression of X-linked genes involved in neuronal development which are probable candidates to regulate Ngn3 and other neuritogenic genes. We evaluated by RT-qPCR the expression of Ddx3x, Eif2s3x, Kdm5c, Kdm6a, Syp, Mecp2 and Usp9x in primary hypothalamic cultures from E15 embryos segregated by gonadal sex and genotype. Ddx3x, Eif2s3x and Kdm6a showed higher levels of expression in XX than in XY neurons (p<0.05), regardless of gonadal type. Since Kdm6a is a histone demethylase that regulates autosomal gene transcription, we decided to focus our study on it. Exogenous administration of 17β-estradiol (10-10 M) did not affect Kdm6a expression in XX/XY neuronal cultures. Moreover, the expression pattern of Kdm6a mRNA in ventromedial hypothalamic region varied with age: only XX males showed higher levels of Kdm6a than the other genotypes in hypothalami of adults. Finally, we evaluated the effect of Kdm6a/b activity inhibitor GSK-J4 on the sexually dimorphic expression of Ngn3. Our results indicated that GSK-J4 diminished Ngn3 expression only in XX neurons, independently of gonadal type. Altogether, these results point to Kdm6a as a regulator of Ngn3, and encourage to continuing with further experiments in order to better understand its role in the generation of sex differences in the developing brain. Financial support: CONICET, ANPCyT, and SECyT-UNC, Argentina; BFU2017-82754-R and MHE-200057, Spain.
Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cabrera Zapata, Lucas Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.
Fil: Arévalo, María Ángeles. Instituto Cajal; España.
Fil: Arévalo, María Ángeles. Instituto de Salud Carlos III; España.
Fil: Garcia-Segura, Luis Miguel. Instituto Cajal; España.
Fil: Garcia-Segura, Luis Miguel. Instituto de Salud Carlos III; España.
Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.
Neurociencias (incluye Psicofiosiología)
Materia
kdm6a
Gondal sex
Ngn3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Repositorio Digital Universitario (UNC)
Institución
Universidad Nacional de Córdoba
OAI Identificador
oai:rdu.unc.edu.ar:11086/556331
Acceder
id RDUUNC_44ba84297d8b5925c5ce83c592b429cb
oai_identifier_str oai:rdu.unc.edu.ar:11086/556331
network_acronym_str RDUUNC
repository_id_str 2572
network_name_str Repositorio Digital Universitario (UNC)
spelling X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brainCabrera Zapata, L. E.Arevalo, M. A.Garcia-Segura, L. M.Cambiasso, M. J.kdm6aGondal sexNgn3Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Cabrera Zapata, Lucas Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Arévalo, María Ángeles. Instituto Cajal; España.Fil: Arévalo, María Ángeles. Instituto de Salud Carlos III; España.Fil: Garcia-Segura, Luis Miguel. Instituto Cajal; España.Fil: Garcia-Segura, Luis Miguel. Instituto de Salud Carlos III; España.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Several X-linked genes are involved in neuronal growth and differentiation and may contribute to the generation of sex differences in brain. Previous results showed that XX hypothalamic neurons grow at a faster rate of development and exhibit higher expression of the neuritogenic gen neurogenin 3 (Ngn3) than XY neurons, independently of gonadal hormones. Since Ngn3 is an autosomal gene, such sex differences should be consequence of differences in the expression of X or Y chromosome genes. Using the Four Core Genotypes mouse model, we analyzed the expression of X-linked genes involved in neuronal development which are probable candidates to regulate Ngn3 and other neuritogenic genes. We evaluated by RT-qPCR the expression of Ddx3x, Eif2s3x, Kdm5c, Kdm6a, Syp, Mecp2 and Usp9x in primary hypothalamic cultures from E15 embryos segregated by gonadal sex and genotype. Ddx3x, Eif2s3x and Kdm6a showed higher levels of expression in XX than in XY neurons (p<0.05), regardless of gonadal type. Since Kdm6a is a histone demethylase that regulates autosomal gene transcription, we decided to focus our study on it. Exogenous administration of 17&#946;-estradiol (10-10 M) did not affect Kdm6a expression in XX/XY neuronal cultures. Moreover, the expression pattern of Kdm6a mRNA in ventromedial hypothalamic region varied with age: only XX males showed higher levels of Kdm6a than the other genotypes in hypothalami of adults. Finally, we evaluated the effect of Kdm6a/b activity inhibitor GSK-J4 on the sexually dimorphic expression of Ngn3. Our results indicated that GSK-J4 diminished Ngn3 expression only in XX neurons, independently of gonadal type. Altogether, these results point to Kdm6a as a regulator of Ngn3, and encourage to continuing with further experiments in order to better understand its role in the generation of sex differences in the developing brain. Financial support: CONICET, ANPCyT, and SECyT-UNC, Argentina; BFU2017-82754-R and MHE-200057, Spain.Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Cabrera Zapata, Lucas Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Arévalo, María Ángeles. Instituto Cajal; España.Fil: Arévalo, María Ángeles. Instituto de Salud Carlos III; España.Fil: Garcia-Segura, Luis Miguel. Instituto Cajal; España.Fil: Garcia-Segura, Luis Miguel. Instituto de Salud Carlos III; España.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Neurociencias (incluye Psicofiosiología)2019info:eu-repo/semantics/conferenceObjectinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfhttp://hdl.handle.net/11086/556331enginfo:eu-repo/semantics/openAccessreponame:Repositorio Digital Universitario (UNC)instname:Universidad Nacional de Córdobainstacron:UNC2025-10-23T11:18:24Zoai:rdu.unc.edu.ar:11086/556331Institucionalhttps://rdu.unc.edu.ar/Universidad públicaNo correspondehttp://rdu.unc.edu.ar/oai/snrdoca.unc@gmail.comArgentinaNo correspondeNo correspondeNo correspondeopendoar:25722025-10-23 11:18:24.724Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdobafalse
dc.title.none.fl_str_mv X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
title X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
spellingShingle X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
Cabrera Zapata, L. E.
kdm6a
Gondal sex
Ngn3
title_short X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
title_full X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
title_fullStr X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
title_full_unstemmed X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
title_sort X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
dc.creator.none.fl_str_mv Cabrera Zapata, L. E.
Arevalo, M. A.
Garcia-Segura, L. M.
Cambiasso, M. J.
author Cabrera Zapata, L. E.
author_facet Cabrera Zapata, L. E.
Arevalo, M. A.
Garcia-Segura, L. M.
Cambiasso, M. J.
author_role author
author2 Arevalo, M. A.
Garcia-Segura, L. M.
Cambiasso, M. J.
author2_role author
author
author
dc.subject.none.fl_str_mv kdm6a
Gondal sex
Ngn3
topic kdm6a
Gondal sex
Ngn3
dc.description.none.fl_txt_mv Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cabrera Zapata, Lucas Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.
Fil: Arévalo, María Ángeles. Instituto Cajal; España.
Fil: Arévalo, María Ángeles. Instituto de Salud Carlos III; España.
Fil: Garcia-Segura, Luis Miguel. Instituto Cajal; España.
Fil: Garcia-Segura, Luis Miguel. Instituto de Salud Carlos III; España.
Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.
Several X-linked genes are involved in neuronal growth and differentiation and may contribute to the generation of sex differences in brain. Previous results showed that XX hypothalamic neurons grow at a faster rate of development and exhibit higher expression of the neuritogenic gen neurogenin 3 (Ngn3) than XY neurons, independently of gonadal hormones. Since Ngn3 is an autosomal gene, such sex differences should be consequence of differences in the expression of X or Y chromosome genes. Using the Four Core Genotypes mouse model, we analyzed the expression of X-linked genes involved in neuronal development which are probable candidates to regulate Ngn3 and other neuritogenic genes. We evaluated by RT-qPCR the expression of Ddx3x, Eif2s3x, Kdm5c, Kdm6a, Syp, Mecp2 and Usp9x in primary hypothalamic cultures from E15 embryos segregated by gonadal sex and genotype. Ddx3x, Eif2s3x and Kdm6a showed higher levels of expression in XX than in XY neurons (p<0.05), regardless of gonadal type. Since Kdm6a is a histone demethylase that regulates autosomal gene transcription, we decided to focus our study on it. Exogenous administration of 17&#946;-estradiol (10-10 M) did not affect Kdm6a expression in XX/XY neuronal cultures. Moreover, the expression pattern of Kdm6a mRNA in ventromedial hypothalamic region varied with age: only XX males showed higher levels of Kdm6a than the other genotypes in hypothalami of adults. Finally, we evaluated the effect of Kdm6a/b activity inhibitor GSK-J4 on the sexually dimorphic expression of Ngn3. Our results indicated that GSK-J4 diminished Ngn3 expression only in XX neurons, independently of gonadal type. Altogether, these results point to Kdm6a as a regulator of Ngn3, and encourage to continuing with further experiments in order to better understand its role in the generation of sex differences in the developing brain. Financial support: CONICET, ANPCyT, and SECyT-UNC, Argentina; BFU2017-82754-R and MHE-200057, Spain.
Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cabrera Zapata, Lucas Ezequiel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.
Fil: Arévalo, María Ángeles. Instituto Cajal; España.
Fil: Arévalo, María Ángeles. Instituto de Salud Carlos III; España.
Fil: Garcia-Segura, Luis Miguel. Instituto Cajal; España.
Fil: Garcia-Segura, Luis Miguel. Instituto de Salud Carlos III; España.
Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.
Neurociencias (incluye Psicofiosiología)
description Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/conferenceObject
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
format conferenceObject
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11086/556331
url http://hdl.handle.net/11086/556331
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositorio Digital Universitario (UNC)
instname:Universidad Nacional de Córdoba
instacron:UNC
reponame_str Repositorio Digital Universitario (UNC)
collection Repositorio Digital Universitario (UNC)
instname_str Universidad Nacional de Córdoba
instacron_str UNC
institution UNC
repository.name.fl_str_mv Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdoba
repository.mail.fl_str_mv oca.unc@gmail.com
_version_ 1846785304773525504
score 12.982451

Publicaciones similares