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The interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis

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dc.contributor.author Belzunce Guillermo, Ivan, 1992-
dc.contributor.author Belmonte Mateos, Carla, 1992-
dc.contributor.author Pujades Corbi, Cristina
dc.date.accessioned 2020-04-22T06:55:18Z
dc.date.available 2020-04-22T06:55:18Z
dc.date.issued 2020
dc.identifier.citation Belzunce I, Belmonte-Mateos C, Pujades C. The interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis. PLoS One. 2020; 15(2):e0228225. DOI: 10.1371/journal.pone.0228225
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/44306
dc.description.abstract The Lower Rhombic Lip (LRL) is a transient neuroepithelial structure of the dorsal hindbrain, which expands from r2 to r7, and gives rise to deep nuclei of the brainstem, such as the vestibular and auditory nuclei and most posteriorly the precerebellar nuclei. Although there is information about the contribution of specific proneural-progenitor populations to specific deep nuclei, and the distinct rhombomeric contribution, little is known about how progenitor cells from the LRL behave during neurogenesis and how their transition into differentiation is regulated. In this work, we investigated the atoh1 gene regulatory network operating in the specification of LRL cells, and the kinetics of cell proliferation and behavior of atoh1a-derivatives by using complementary strategies in the zebrafish embryo. We unveiled that atoh1a is necessary and sufficient for specification of LRL cells by activating atoh1b, which worked as a differentiation gene to transition progenitor cells towards neuron differentiation in a Notch-dependent manner. This cell state transition involved the release of atoh1a-derivatives from the LRL: atoh1a progenitors contributed first to atoh1b cells, which are committed non-proliferative precursors, and to the lhx2b-neuronal lineage as demonstrated by cell fate studies and functional analyses. Using in vivo cell lineage approaches we revealed that the proliferative cell capacity, as well as the mode of division, relied on the position of the atoh1a progenitors within the dorsoventral axis. We showed that atoh1a may behave as the cell fate selector gene, whereas atoh1b functions as a neuronal differentiation gene, contributing to the lhx2b neuronal population. atoh1a-progenitor cell dynamics (cell proliferation, cell differentiation, and neuronal migration) relies on their position, demonstrating the challenges that progenitor cells face in computing positional information from a dynamic two-dimensional grid in order to generate the stereotyped neuronal structures in the embryonic hindbrain.
dc.description.sponsorship This work was supported by BFU2016-81887-REDT/AEI (MINECO-FEDER), and AEI-PGC2018-095663-B-I00 FEDER/UE (MICIU) to CP, and Unidad de Excelencia María de Maetzu MDM-2014-0370 and AEI-CEX2018-000792-M to DCEXS-UPF. IB and CBM were recipients of predoctoral fellowships from the Generalitat de Catalunya (FI) and the Spanish Ministry of Economy, Industry and Competitiveness (FPI), respectively. CP is a recipient of ICREA Academia award (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS One. 2020; 15(2):e0228225
dc.rights © 2020 Belzunce et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title The interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0228225
dc.subject.keyword Neuronal differentiation
dc.subject.keyword Embryos
dc.subject.keyword Neurons
dc.subject.keyword Hindbrain
dc.subject.keyword Stem cells
dc.subject.keyword Cell cycle and cell division
dc.subject.keyword Cell differentiation
dc.subject.keyword In situ hybridization
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-81887
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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