Conservation of different mechanisms of Hox cluster regulation within chordates

Departament responsable de la tesi: Departament de Genètica

Detalles Bibliográficos
Autor: Herrera Úbeda, Carlos
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/668561
Acceso en línea:http://hdl.handle.net/10803/668561
Access Level:acceso abierto
Palabra clave:Genòmica
Genómica
Genomics
Cordats
Cordados
Chordata
Genètica evolutiva
Genética evolutiva
Evolutionary genetics
Ciències Experimentals i Matemàtiques
575
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spelling Conservation of different mechanisms of Hox cluster regulation within chordatesHerrera Úbeda, CarlosGenòmicaGenómicaGenomicsCordatsCordadosChordataGenètica evolutivaGenética evolutivaEvolutionary geneticsCiències Experimentals i Matemàtiques575Departament responsable de la tesi: Departament de GenèticaIn this thesis we have covered the importance of finding underlying conservation events to better understand the regulatory mechanisms of important development orchestrators like the Hox cluster. As an example of these non-evident conservation, we have shown two cases, as described below. The first case studied, after developing a software able to detect homologous long noncoding RNAs by means of microsynteny analyses, is the conservation of Hotairm1 in Chordata. For assessing the homology of this lncRNA, first we had to identify the lncRNA fraction within the B. lanceolatum transcriptome. With a reliable lincRNA dataset, we used our pipeline, LincOFinder, to identify orthologs between human and amphioxus through microsynteny. After the identification of Hotairm1 as one of the lincRNAs with conserved microsynteny, we used Xenopus as a proxy to analyse the homologies in the expression and the function. We had to proceed this way due to the difficulties associated with the inhibition of genes in B. lanceolatum, and the unavailability of expression patterns for Hotairm1 in the bibliography. After we successfully characterised Hotairm1 expression in amphioxus and Xenopus, we injected morpholino oligonucleotides to target and inhibit the splicing of Hotairm1 to promote an isoform imbalance. Through the phenotype obtained and the performing of qPCRs, we were able to deduct the mechanism of Hotairm1 and successfully relate this mechanism with the one described in human cells. With all the data obtained we were able to strongly suggest that the amphioxus Hotairm1 is homologous to the Xenopus and human Hotairm1, thus being conserved in most of the lineages within chordates. The second case studied was the conservation of the regulation of the Hox cluster mediated by Cdx. When analysing the B. floridae knockouts of Cdx and Pdx obtained using the TALEN technique, we found a severe phenotype of the developing larvae in Cdx-/- and a mild phenotype in Pdx-/-. The Cdx-/- phenotype consisted in the disruption of posterior gut development, as well as an underdevelopment of the postanal tail, coupled with a non-opening anus. When looking at changes in the expression of the Hox cluster in this Cdx-/- embryos, we found collinear misregulation of the expressed Hox genes, with the most anterior Hox cluster genes upregulated, and the most posterior ones downregulated. This is very similar to findings seen in triple morpholino knockdowns of the Cdx genes in Xenopus, indicating that in both, Xenopus and amphioxus, Cdx is regulating the Hox cluster through a homologous mechanism.Universitat de BarcelonaGarcia Fernández, JordiGarcia Fernández, JordiUniversitat de Barcelona. Departament de Genètica, Microbiologia i Estadística202020202019info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion196 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/668561TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-sa/4.0/http://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6685612026-06-14T12:46:07Z
dc.title.none.fl_str_mv Conservation of different mechanisms of Hox cluster regulation within chordates
title Conservation of different mechanisms of Hox cluster regulation within chordates
spellingShingle Conservation of different mechanisms of Hox cluster regulation within chordates
Herrera Úbeda, Carlos
Genòmica
Genómica
Genomics
Cordats
Cordados
Chordata
Genètica evolutiva
Genética evolutiva
Evolutionary genetics
Ciències Experimentals i Matemàtiques
575
title_short Conservation of different mechanisms of Hox cluster regulation within chordates
title_full Conservation of different mechanisms of Hox cluster regulation within chordates
title_fullStr Conservation of different mechanisms of Hox cluster regulation within chordates
title_full_unstemmed Conservation of different mechanisms of Hox cluster regulation within chordates
title_sort Conservation of different mechanisms of Hox cluster regulation within chordates
dc.creator.none.fl_str_mv Herrera Úbeda, Carlos
author Herrera Úbeda, Carlos
author_facet Herrera Úbeda, Carlos
author_role author
dc.contributor.none.fl_str_mv Garcia Fernández, Jordi
Garcia Fernández, Jordi
Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística
dc.subject.none.fl_str_mv Genòmica
Genómica
Genomics
Cordats
Cordados
Chordata
Genètica evolutiva
Genética evolutiva
Evolutionary genetics
Ciències Experimentals i Matemàtiques
575
topic Genòmica
Genómica
Genomics
Cordats
Cordados
Chordata
Genètica evolutiva
Genética evolutiva
Evolutionary genetics
Ciències Experimentals i Matemàtiques
575
description Departament responsable de la tesi: Departament de Genètica
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/668561
url http://hdl.handle.net/10803/668561
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 196 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407045743017984
score 15,300719

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