Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling

The key molecular interactions governing vertebrate limb bud development are a paradigm for studying the mechanisms controlling progenitor cell proliferation and specification during vertebrate organogenesis. However, little is known about the cellular heterogeneity of the mesenchymal progenitors in...

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Autores: Reinhardt, Robert, Gullotta, Fabiana, Nusspaumer, Gretel, Ünal, Erkan, Ivanek, Robert, Zuniga, Aimée, Zeller, Rolf
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/209502
Acceso en línea:http://hdl.handle.net/10261/209502
Access Level:acceso abierto
Palabra clave:Cell sorting
Chondrogenesis
Mesenchymal progenitors
Mouse limb bud
Signaling
Transcriptomes
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spelling Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signalingReinhardt, RobertGullotta, FabianaNusspaumer, GretelÜnal, ErkanIvanek, RobertZuniga, AiméeZeller, RolfCell sortingChondrogenesisMesenchymal progenitorsMouse limb budSignalingTranscriptomesThe key molecular interactions governing vertebrate limb bud development are a paradigm for studying the mechanisms controlling progenitor cell proliferation and specification during vertebrate organogenesis. However, little is known about the cellular heterogeneity of the mesenchymal progenitors in early limb buds that ultimately contribute to the chondrogenic condensations prefiguring the skeleton. We combined flow cytometric and transcriptome analyses to identify the molecular signatures of several distinct mesenchymal progenitor cell populations present in early mouse forelimb buds. In particular, jagged 1 (JAG1)-positive cells located in the posterior-distal mesenchyme were identified as the most immature limb bud mesenchymal progenitors (LMPs), which crucially depend on SHH and FGF signaling in culture. The analysis of gremlin 1 (Grem1)-deficient forelimb buds showed that JAG1-expressing LMPs are protected from apoptosis by GREM1-mediated BMP antagonism. At the same stage, the osteo-chondrogenic progenitors (OCPs) located in the core mesenchyme are already actively responding to BMP signaling. This analysis sheds light on the cellular heterogeneity of the early mouse limb bud mesenchyme and on the distinct response of LMPs and OCPs to morphogen signaling.This work was supported by funds from both the Universität Basel and the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_166685 to A.Z. and R.Z.; 31003A_156430 to R.Z. and Ivan Martin), by a SystemsX iPhD grant (51PH-0_131349 to E.Ü.), and by the Deutsche Forschungsgemeinschaft (RE 3830/2-1 to R.R.). Deposited in PMC for immediate release.Company of BiologistsUniversity of BaselMinistry of Innovation, Science and Research of the State of North Rhine-WestphaliaGerman Research FoundationConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/209502reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1242/dev.173328Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2095022026-05-22T06:33:51Z
dc.title.none.fl_str_mv Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
title Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
spellingShingle Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
Reinhardt, Robert
Cell sorting
Chondrogenesis
Mesenchymal progenitors
Mouse limb bud
Signaling
Transcriptomes
title_short Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
title_full Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
title_fullStr Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
title_full_unstemmed Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
title_sort Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling
dc.creator.none.fl_str_mv Reinhardt, Robert
Gullotta, Fabiana
Nusspaumer, Gretel
Ünal, Erkan
Ivanek, Robert
Zuniga, Aimée
Zeller, Rolf
author Reinhardt, Robert
author_facet Reinhardt, Robert
Gullotta, Fabiana
Nusspaumer, Gretel
Ünal, Erkan
Ivanek, Robert
Zuniga, Aimée
Zeller, Rolf
author_role author
author2 Gullotta, Fabiana
Nusspaumer, Gretel
Ünal, Erkan
Ivanek, Robert
Zuniga, Aimée
Zeller, Rolf
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv University of Basel
Ministry of Innovation, Science and Research of the State of North Rhine-Westphalia
German Research Foundation
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cell sorting
Chondrogenesis
Mesenchymal progenitors
Mouse limb bud
Signaling
Transcriptomes
topic Cell sorting
Chondrogenesis
Mesenchymal progenitors
Mouse limb bud
Signaling
Transcriptomes
description The key molecular interactions governing vertebrate limb bud development are a paradigm for studying the mechanisms controlling progenitor cell proliferation and specification during vertebrate organogenesis. However, little is known about the cellular heterogeneity of the mesenchymal progenitors in early limb buds that ultimately contribute to the chondrogenic condensations prefiguring the skeleton. We combined flow cytometric and transcriptome analyses to identify the molecular signatures of several distinct mesenchymal progenitor cell populations present in early mouse forelimb buds. In particular, jagged 1 (JAG1)-positive cells located in the posterior-distal mesenchyme were identified as the most immature limb bud mesenchymal progenitors (LMPs), which crucially depend on SHH and FGF signaling in culture. The analysis of gremlin 1 (Grem1)-deficient forelimb buds showed that JAG1-expressing LMPs are protected from apoptosis by GREM1-mediated BMP antagonism. At the same stage, the osteo-chondrogenic progenitors (OCPs) located in the core mesenchyme are already actively responding to BMP signaling. This analysis sheds light on the cellular heterogeneity of the early mouse limb bud mesenchyme and on the distinct response of LMPs and OCPs to morphogen signaling.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/209502
url http://hdl.handle.net/10261/209502
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1242/dev.173328
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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