Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity

Mammalian digit tip regeneration is linked to the presence of nail tissue, but a nail-explicit model is missing. Here, we report that nail-less double-ventral digits of dLARM1/2 mutants that lack limb-specific Lmx1b enhancers fail to regenerate. To separate the nail's effect from the lack of do...

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Detalles Bibliográficos
Autores: Castilla-Ibeas, Alejandro, Zdral, Sofía, Galán, Laura, Haro, Endika, Allou, Lila, Campa, Víctor M., Icardo, Jose M., Mundlos, Stefan, Oberg, Kerby C., Ros, María A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/339372
Acceso en línea:http://hdl.handle.net/10261/339372
Access Level:acceso abierto
Palabra clave:Regeneration
Digit tip
Lmx1b
Blastema
Nail
Dorso-ventral patterning
Limb
RNAseq
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spelling Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarityCastilla-Ibeas, AlejandroZdral, SofíaGalán, LauraHaro, EndikaAllou, LilaCampa, Víctor M.Icardo, Jose M.Mundlos, StefanOberg, Kerby C.Ros, María A.RegenerationDigit tipLmx1bBlastemaNailDorso-ventral patterningLimbRNAseqMammalian digit tip regeneration is linked to the presence of nail tissue, but a nail-explicit model is missing. Here, we report that nail-less double-ventral digits of dLARM1/2 mutants that lack limb-specific Lmx1b enhancers fail to regenerate. To separate the nail's effect from the lack of dorsoventral (DV) polarity, we also interrogate double-dorsal double-nail digits and show that they regenerate. Thus, DV polarity is not a prerequisite for regeneration, and the nail requirement is supported. Transcriptomic comparison between wild-type and non-regenerative dLARM1/2 mutant blastemas reveals differential upregulation of vascularization and connective tissue functional signatures in wild type versus upregulation of inflammation in the mutant. These results, together with the finding of Lmx1b expression in the postnatal dorsal dermis underneath the nail and uniformly in the regenerative blastema, open the possibility of additional Lmx1b roles in digit tip regeneration, in addition to the indirect effect of mediating the formation of the nail.Supported by funds from the Spanish Ministry of Science and Innovation Grant PID2020-114525GB-I00 to M.R. and from the Pathology Research endowment, the S. H. Crook’s Chair to K.C.O. A.C.-I. is supported by Spanish Ministry of Science and Innovation PhD fellowship PRE2018-083421. S.Z. was supported by a PhD fellowship from the Universidad de Cantabria. SHG imaging and analysis was conducted at the Microscopy & Dynamic Imaging Unit, CNIC, ICTS-ReDib, co-funded by MCIN/AEI/10.13039/501100011033.Peer reviewedCell PressMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Ministerio de Economía y Competitividad (España)Universidad de CantabriaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/339372reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#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/PID2020-114525GB-I00info:eu-repo/grantAgreement/AEI//PRE2018-083421Castilla-Ibeas, Alejandro; Zdral, Sofía; Galán, Laura; Haro, Endika; Allou, Lila; Campa, Víctor M.; Icardo, Jose M.; Mundlos, Stefan; Oberg, Kerby C.; Ros, María A.; 2023; Supplemental Material for “Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity” [Dataset]; Elsevier; https://doi.org/10.1016/j.celrep.2022.111975http://dx.doi.org/10.1016/j.celrep.2022.111975Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3393722026-05-22T06:33:51Z
dc.title.none.fl_str_mv Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
title Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
spellingShingle Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
Castilla-Ibeas, Alejandro
Regeneration
Digit tip
Lmx1b
Blastema
Nail
Dorso-ventral patterning
Limb
RNAseq
title_short Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
title_full Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
title_fullStr Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
title_full_unstemmed Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
title_sort Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity
dc.creator.none.fl_str_mv Castilla-Ibeas, Alejandro
Zdral, Sofía
Galán, Laura
Haro, Endika
Allou, Lila
Campa, Víctor M.
Icardo, Jose M.
Mundlos, Stefan
Oberg, Kerby C.
Ros, María A.
author Castilla-Ibeas, Alejandro
author_facet Castilla-Ibeas, Alejandro
Zdral, Sofía
Galán, Laura
Haro, Endika
Allou, Lila
Campa, Víctor M.
Icardo, Jose M.
Mundlos, Stefan
Oberg, Kerby C.
Ros, María A.
author_role author
author2 Zdral, Sofía
Galán, Laura
Haro, Endika
Allou, Lila
Campa, Víctor M.
Icardo, Jose M.
Mundlos, Stefan
Oberg, Kerby C.
Ros, María A.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Ministerio de Economía y Competitividad (España)
Universidad de Cantabria
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Regeneration
Digit tip
Lmx1b
Blastema
Nail
Dorso-ventral patterning
Limb
RNAseq
topic Regeneration
Digit tip
Lmx1b
Blastema
Nail
Dorso-ventral patterning
Limb
RNAseq
description Mammalian digit tip regeneration is linked to the presence of nail tissue, but a nail-explicit model is missing. Here, we report that nail-less double-ventral digits of dLARM1/2 mutants that lack limb-specific Lmx1b enhancers fail to regenerate. To separate the nail's effect from the lack of dorsoventral (DV) polarity, we also interrogate double-dorsal double-nail digits and show that they regenerate. Thus, DV polarity is not a prerequisite for regeneration, and the nail requirement is supported. Transcriptomic comparison between wild-type and non-regenerative dLARM1/2 mutant blastemas reveals differential upregulation of vascularization and connective tissue functional signatures in wild type versus upregulation of inflammation in the mutant. These results, together with the finding of Lmx1b expression in the postnatal dorsal dermis underneath the nail and uniformly in the regenerative blastema, open the possibility of additional Lmx1b roles in digit tip regeneration, in addition to the indirect effect of mediating the formation of the nail.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
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/10261/339372
url http://hdl.handle.net/10261/339372
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #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/PID2020-114525GB-I00
info:eu-repo/grantAgreement/AEI//PRE2018-083421
Castilla-Ibeas, Alejandro; Zdral, Sofía; Galán, Laura; Haro, Endika; Allou, Lila; Campa, Víctor M.; Icardo, Jose M.; Mundlos, Stefan; Oberg, Kerby C.; Ros, María A.; 2023; Supplemental Material for “Failure of digit tip regeneration in the absence of Lmx1b suggests Lmx1b functions disparate from dorsoventral polarity” [Dataset]; Elsevier; https://doi.org/10.1016/j.celrep.2022.111975
http://dx.doi.org/10.1016/j.celrep.2022.111975
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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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