X-linked histone demethylase kdm6a as a candidate to mediate sex chromosome effects on Ngn3 dimorphic expression in the developing brain
Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
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| Format: | conferenceObject |
| Language: | eng |
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2025
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| Online Access: | http://hdl.handle.net/11086/556331 |
| _version_ | 1837938393317638144 |
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| author | Cabrera Zapata, L. E. Arevalo, M. A. Garcia-Segura, L. M. Cambiasso, M. J. |
| author_facet | Cabrera Zapata, L. E. Arevalo, M. A. Garcia-Segura, L. M. Cambiasso, M. J. |
| author_sort | Cabrera Zapata, L. E. |
| collection | Repositorio Digital Universitario |
| description | Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. |
| format | conferenceObject |
| id | rdu-unc.556331 |
| institution | Universidad Nacional de Cordoba |
| language | eng |
| publishDate | 2025 |
| record_format | dspace |
| spelling | rdu-unc.5563312025-07-16T21:08:34Z 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. Arevalo, M. A. Garcia-Segura, L. M. Cambiasso, M. J. kdm6a Gondal sex Ngn3 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) 2025-07-03T14:39:48Z 2025-07-03T14:39:48Z 2019 conferenceObject http://hdl.handle.net/11086/556331 eng Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0/ Impreso |
| spellingShingle | kdm6a Gondal sex Ngn3 Cabrera Zapata, L. E. Arevalo, M. A. Garcia-Segura, L. M. Cambiasso, M. J. 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 |
| 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_short | 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 |
| topic | kdm6a Gondal sex Ngn3 |
| url | http://hdl.handle.net/11086/556331 |
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