Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2024.1464932/full#supplementary-material
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/380279 |
| Acceso en línea: | http://hdl.handle.net/10261/380279 https://api.elsevier.com/content/abstract/scopus_id/85206077776 |
| Access Level: | acceso abierto |
| Palabra clave: | DNp73 TAp73 Brain development Brain morphogenesis Mouse brain organoids Neurogenesis p53-family p73 |
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Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| title |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| spellingShingle |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate Alonso-Olivares, Hugo DNp73 TAp73 Brain development Brain morphogenesis Mouse brain organoids Neurogenesis p53-family p73 |
| title_short |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| title_full |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| title_fullStr |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| title_full_unstemmed |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| title_sort |
Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fate |
| dc.creator.none.fl_str_mv |
Alonso-Olivares, Hugo Marques, Margarita M. Prieto-Colomina, Anna López-Ferreras, Lorena Martínez-García, Nicole Vázquez-Jiménez, Alberto Borrell, Víctor Marín, María C. Fernández-Alonso, Rosalía |
| author |
Alonso-Olivares, Hugo |
| author_facet |
Alonso-Olivares, Hugo Marques, Margarita M. Prieto-Colomina, Anna López-Ferreras, Lorena Martínez-García, Nicole Vázquez-Jiménez, Alberto Borrell, Víctor Marín, María C. Fernández-Alonso, Rosalía |
| author_role |
author |
| author2 |
Marques, Margarita M. Prieto-Colomina, Anna López-Ferreras, Lorena Martínez-García, Nicole Vázquez-Jiménez, Alberto Borrell, Víctor Marín, María C. Fernández-Alonso, Rosalía |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) Junta de Castilla y León European Commission European Research Council Fundación Científica Asociación Española Contra el Cáncer Asociación Española Contra el Cáncer Fundación Tatiana Pérez de Guzmán el Bueno Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
DNp73 TAp73 Brain development Brain morphogenesis Mouse brain organoids Neurogenesis p53-family p73 |
| topic |
DNp73 TAp73 Brain development Brain morphogenesis Mouse brain organoids Neurogenesis p53-family p73 |
| description |
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2024.1464932/full#supplementary-material |
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2024 |
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2024 2025 2025 |
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info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/380279 https://api.elsevier.com/content/abstract/scopus_id/85206077776 |
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http://hdl.handle.net/10261/380279 https://api.elsevier.com/content/abstract/scopus_id/85206077776 |
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Inglés |
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Inglés |
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#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105169RB-I00 info:eu‐repo/grantAgreement/ERC//101118729 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001165-S The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.3389/fcell.2024.1464932 https://doi.org/10.3389/fcell.2024.1464932 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Frontiers Media |
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Frontiers Media |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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Mouse cortical organoids reveal key functions of p73 isoforms: TAp73 governs the establishment of the archetypical ventricular-like zones while DNp73 is central in the regulation of neural cell fateAlonso-Olivares, HugoMarques, Margarita M.Prieto-Colomina, AnnaLópez-Ferreras, LorenaMartínez-García, NicoleVázquez-Jiménez, AlbertoBorrell, VíctorMarín, María C.Fernández-Alonso, RosalíaDNp73TAp73Brain developmentBrain morphogenesisMouse brain organoidsNeurogenesisp53-familyp73The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2024.1464932/full#supplementary-material[Introduction] Neurogenesis is tightly regulated in space and time, ensuring the correct development and organization of the central nervous system. Critical regulators of brain development and morphogenesis in mice include two members of the p53 family: p53 and p73. However, dissecting the in vivo functions of these factors and their various isoforms in brain development is challenging due to their pleiotropic effects. Understanding their role, particularly in neurogenesis and brain morphogenesis, requires innovative experimental approaches.[Methods] To address these challenges, we developed an efficient and highly reproducible protocol to generate mouse brain organoids from pluripotent stem cells. These organoids contain neural progenitors and neurons that self-organize into rosette-like structures resembling the ventricular zone of the embryonic forebrain. Using this model, we generated organoids from p73-deficient mouse cells to investigate the roles of p73 and its isoforms (TA and DNp73) during brain development.[Results and Discussion] Organoids derived from p73-deficient cells exhibited increased neuronal apoptosis and reduced neural progenitor proliferation, linked to compensatory activation of p53. This closely mirrors previous in vivo observations, confirming that p73 plays a pivotal role in brain development. Further dissection of p73 isoforms function revealed a dual role of p73 in regulating brain morphogenesis, whereby TAp73 controls transcriptional programs essential for the establishment of the neurogenic niche structure, while DNp73 is responsible for the precise and timely regulation of neural cell fate. These findings highlight the distinct roles of p73 isoforms in maintaining the balance of neural progenitor cell biology, providing a new understanding of how p73 regulates brain morphogenesisThe author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Grants PID 2019-105169RB-I00 funded by MCIN/AEI/10.13039/501100011033 and LE022P20 from Junta de Castilla y León (cofinanced with FEDER funds) (to MCM), and by European Research Council (101118729) to VB, who also acknowledges financial support from the AEI through the “Severo Ochoa” Program for Centers of Excellence in R&D (CEX2021-001165-S funded by MCIN/AEI/10.13039/501100011033). Fundación Asociación Española Contra el Cáncer grant (PRYGN21941BORR). RF-A was supported by a María Zambrano fellowship from AEI. HA-O and NM-G are supported by a predoctoral scholarship from the Asociación Española Contra el Cáncer (AECC), and AP-C was supported by a Fundación Tatiana Pérez de Guzmán el Bueno fellowship.With funding from the Spanish government through the "Severo Ochoa Centre of Excelence" accreditation (CEX2021-001165-S)Peer reviewedFrontiers MediaMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Junta de Castilla y LeónEuropean CommissionEuropean Research CouncilFundación Científica Asociación Española Contra el CáncerAsociación Española Contra el CáncerFundación Tatiana Pérez de Guzmán el BuenoConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/380279https://api.elsevier.com/content/abstract/scopus_id/85206077776reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105169RB-I00info:eu‐repo/grantAgreement/ERC//101118729info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001165-SThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.3389/fcell.2024.1464932https://doi.org/10.3389/fcell.2024.1464932Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3802792026-05-22T06:33:51Z |
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15,81155 |