Her9 controls the stemness properties of hindbrain boundary cells
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- dc.contributor.author Engel-Pizcueta, Carolyn
- dc.contributor.author Hevia, Covadonga F.
- dc.contributor.author Voltes Cobo, Adrià
- dc.contributor.author Livet, Jean
- dc.contributor.author Pujades Corbi, Cristina
- dc.date.accessioned 2025-02-20T13:01:47Z
- dc.date.available 2025-02-20T13:01:47Z
- dc.date.issued 2025
- dc.description.abstract The different spatiotemporal distribution of progenitor and neurogenic capacities permits that brain regions engage asynchronously in neurogenesis. In the hindbrain, rhombomere progenitor cells contribute to neurons during the first neurogenic phase, whereas boundary cells participate later. To analyze what maintains boundary cells as non-neurogenic progenitors, we addressed the role of Her9, a zebrafish Hes1-related protein. her9 expression is temporarily sustained in boundary cells independently of Notch at early embryonic stages, while they are non-neurogenic progenitors. Complementary functional approaches show that Her9 inhibits the onset of Notch signaling and the neurogenic program, keeping boundary cells as progenitors. Multicolor clonal analysis combined with genetic perturbations reveal that Her9 expands boundary progenitors by promoting symmetric proliferative and preventing neurogenic cell divisions. Her9 also regulates the proliferation of boundary cells by inhibiting the cell cycle arrest gene cdkn1ca and interplaying with Cyclin D1. Moreover, her9 is enriched in hindbrain radial glial cells at late embryonic stages independently of Notch. Together these data demonstrate that Her9 maintains the stemness properties of hindbrain boundary progenitors and late radial glial cells, ensuring the different temporal distribution of neurogenic capacities within the hindbrain.
- dc.description.sponsorship This work was funded by grants PGC2018-095663-B-I00 and PID2021-123261NB-I00 from the Agencia Estatal de Investigación (AEI) and the European Regional Development Fund (FEDER) to C.P. The Department of Medicine and Life Sciences (UPF) is a Unidad de Excelencia Maria de Maeztu (CEX2018 000792M) funded by the AEI. This work was also supported by IHU FOReSIGHT/Agence Nationale de la Recherche (ANR-18-IAHU-01 to J.L.). C.E.-P. was a recipient of FPU predoctoral fellowship from the MICIU, and A.V. holds a predoctoral fellowship from 'la Caixa' Foundation. C.P. is a recipient of an Institució Catalana de Recerca i Estudis Avançats (ICREA) Academia award (Generalitat de Catalunya). Open Access funding provided by Universitat Pompeu Fabra. Deposited in PMC for immediate release.
- dc.format.mimetype application/pdf
- dc.identifier.citation Engel-Pizcueta C, Hevia CF, Voltes A, Livet J, Pujades C. Her9 controls the stemness properties of hindbrain boundary cells. Development. 2025 Jan 1;152(1):dev203164. DOI: 10.1242/dev.203164
- dc.identifier.doi http://dx.doi.org/10.1242/dev.203164
- dc.identifier.issn 0950-1991
- dc.identifier.uri http://hdl.handle.net/10230/69657
- dc.language.iso eng
- dc.publisher Company of Biologists
- dc.relation.ispartof Development. 2025 Jan 1;152(1):dev203164
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-095663-B-I00
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-123261NB-I00
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792M
- dc.rights © 2025. Published by The Company of Biologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0
- dc.subject.keyword Her9
- dc.subject.keyword Hindbrain boundaries
- dc.subject.keyword Multicolor clonal analysis
- dc.subject.keyword Neural progenitors
- dc.subject.keyword Zebrafish
- dc.subject.keyword zebrabow2.0
- dc.title Her9 controls the stemness properties of hindbrain boundary cells
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion