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In a zebrafish biomedical model of human Allan-Herndon-Dudley syndrome impaired MTH signaling leads to decreased neural cell diversity

2023Journal article Open Access
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dc.contributor.authorSilva, Nadia
dc.contributor.authorCampinho, Marco António
dc.date.accessioned2023-06-21T09:59:30Z
dc.date.available2023-06-21T09:59:30Z
dc.date.issued2023
dc.description.abstractMaternally derived thyroid hormone (T3) is a fundamental factor for vertebrate neurodevelopment. In humans, mutations on the thyroid hormones (TH) exclusive transporter monocarboxylic acid transporter 8 (MCT8) lead to the Allan-Herndon-Dudley syndrome (AHDS). Patients with AHDS present severe underdevelopment of the central nervous system, with profound cognitive and locomotor consequences. Functional impairment of zebrafish T3 exclusive membrane transporter Mct8 phenocopies many symptoms observed in patients with AHDS, thus providing an outstanding animal model to study this human condition. In addition, it was previously shown in the zebrafish mct8 KD model that maternal T3 (MTH) acts as an integrator of different key developmental pathways during zebrafish development. MethodsUsing a zebrafish Mct8 knockdown model, with consequent inhibition of maternal thyroid hormones (MTH) uptake to the target cells, we analyzed genes modulated by MTH by qPCR in a temporal series from the start of segmentation through hatching. Survival (TUNEL) and proliferation (PH3) of neural progenitor cells (dla, her2) were determined, and the cellular distribution of neural MTH-target genes in the spinal cord during development was characterized. In addition, in-vivo live imaging was performed to access NOTCH overexpression action on cell division in this AHDS model. We determined the developmental time window when MTH is required for appropriate CNS development in the zebrafish; MTH is not involved in neuroectoderm specification but is fundamental in the early stages of neurogenesis by promoting the maintenance of specific neural progenitor populations. MTH signaling is required for developing different neural cell types and maintaining spinal cord cytoarchitecture, and modulation of NOTCH signaling in a non-autonomous cell manner is involved in this process. DiscussionThe findings show that MTH allows the enrichment of neural progenitor pools, regulating the cell diversity output observed by the end of embryogenesis and that Mct8 impairment restricts CNS development. This work contributes to the understanding of the cellular mechanisms underlying human AHDS.pt_PT
dc.description.sponsorshipALG-01-0145-FEDER-022121; ABC-RI CRESC Algarve 2020pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3389/fendo.2023.1157685pt_PT
dc.identifier.issn1664-2392
dc.identifier.urihttp://hdl.handle.net/10400.1/19721
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Mediapt_PT
dc.relationAlgarve Centre for Marine Sciences
dc.relationMaternal thyroid hormones role in zebrafish neural development
dc.relationUnraveling maternal thyroid hormone role in teleost embryonic development
dc.relationFunctional biology of thyroid hormones in teleost development
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectMaternal thyroid hormonept_PT
dc.subjectMonocarboxylic acid transporter 8pt_PT
dc.subjectNeurodevelopmentpt_PT
dc.subjectSpinal cordpt_PT
dc.subjectZebrafishpt_PT
dc.subjectAllan-Herndon-Dudley syndrome (AHDS)pt_PT
dc.titleIn a zebrafish biomedical model of human Allan-Herndon-Dudley syndrome impaired MTH signaling leads to decreased neural cell diversitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleMaternal thyroid hormones role in zebrafish neural development
oaire.awardTitleUnraveling maternal thyroid hormone role in teleost embryonic development
oaire.awardTitleFunctional biology of thyroid hormones in teleost development
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F111226%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FMAR-BIO%2F0430%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F01274%2F2014%2FCP1217%2FCT0007/PT
oaire.citation.titleFrontiers in Endocrinologypt_PT
oaire.citation.volume14pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStreamInvestigador FCT
person.familyNameSilva
person.familyNameCampinho
person.givenNameNádia
person.givenNameMarco António
person.identifier.ciencia-id5D1F-6F3A-A1C2
person.identifier.ciencia-id0E18-2560-6EC1
person.identifier.orcid0000-0001-9881-4421
person.identifier.orcid0000-0002-5238-0506
person.identifier.ridD-8833-2013
person.identifier.scopus-author-id10244362100
person.identifier.scopus-author-id8938999600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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