The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development.
[eng] Tbx5 is a transcription factor expressed in the developing eyes, heart and upper limbs. Mutations in human TBX5 cause Holt-Oram syndrome (HOS), a condition characterised by heart and upper limb malformations. In zebrafish, a novel tbx5 gene (tbx5b), which emerged from the teleost specific geno...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/124504 |
| Acceso en línea: | https://hdl.handle.net/2445/124504 http://hdl.handle.net/10803/650832 |
| Access Level: | acceso abierto |
| Palabra clave: | Peix zebra Morfogènesi Zebra danio Morphogenesis |
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España |
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| dc.title.none.fl_str_mv |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| title |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| spellingShingle |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. Pi Roig, Aina Peix zebra Morfogènesi Zebra danio Morphogenesis |
| title_short |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| title_full |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| title_fullStr |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| title_full_unstemmed |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| title_sort |
The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development. |
| dc.creator.none.fl_str_mv |
Pi Roig, Aina |
| author |
Pi Roig, Aina |
| author_facet |
Pi Roig, Aina |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Garcia Fernández, Jordi Minguillón Gil, Carolina Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística |
| dc.subject.none.fl_str_mv |
Peix zebra Morfogènesi Zebra danio Morphogenesis |
| topic |
Peix zebra Morfogènesi Zebra danio Morphogenesis |
| description |
[eng] Tbx5 is a transcription factor expressed in the developing eyes, heart and upper limbs. Mutations in human TBX5 cause Holt-Oram syndrome (HOS), a condition characterised by heart and upper limb malformations. In zebrafish, a novel tbx5 gene (tbx5b), which emerged from the teleost specific genome duplication, is co-expressed with its paralogue (tbx5a). To understand tbx5 paralogues function and relationship in the different tissues where they are expressed (i.e. eye, heart and pectoral fin) in zebrafish, downregulation by morpholino oligonucleotides (MO) injection has been performed. The results reveal that tbx5 genes are essential for the development of these organs, where they have different requirements and relationships to ensure proper dorsoventral (DV) retina axis organization, the establishment of cardiac laterality and the induction and sustained outgrowth of the pectoral fin. In the retina, tbx5 genes role is redundant and both paralogues knock-down causes a reduction of the dorsal retina identity, concomitant with an expansion of the ventral retina markers expression, that results in defective DV patterning and subsequent thinner retinotectal projections. In contrast, tbx5a and tbx5b have gene-specific functions during pectoral fin development: tbx5a is required for the initiation of pectoral fin outgrowth, whereas tbx5b is later responsible for the sustained outgrowth of the pectoral fin. In the case of heart morphogenesis, both paralogues cooperate in the same pathway. In addition, our results uncover a novel role for tbx5 paralogues in the establishment of heart asymmetry in zebrafish embryos in both asymmetric events (i.e. cardiac jogging and looping) and an earlier role for tbx5a during the directional migration and of the cardiac precursors in the midline. Further analysis of the role of tbx5a during the establishment of left-right (LR) asymmetry shows that the expression of left-side markers from the Nodal signalling pathway expressed in the lateral plate mesoderm (LPM) is also randomized. Laterality defects during zebrafish development in tbx5a morphant are also found in neural and visceral laterality, suggesting an early role of tbx5a in LR establishment. Strikingly, tbx5a knock-down in the DFCs/KV (dorsal forerunner cells / Kupffer’s vesicle) lineage, the organ responsible for LR asymmetry generation, also results in cardiac jogging randomization. Furthermore, our results show an early tbx5a expression during gastrulation and an altered expression pattern for charon and a reduction on bmp4 expression levels around the KV at 10SS. In addition, a reduction on Bmp signalling levels in tbx5a DFC-specific morphants is detected, which is consistent with the identification of a putative binding site for Tbx5 that is conserved in high vertebrates for bmp2b and bmp4. Finally, the analysis of tbx5a morphants also show that they have a reduced KV. Overall, we propose a model in which tbx5 is required during zebrafish early development to achieve a proper KV size that will ensure a robust directional flow within the KV and Bmp signalling in the KV itself and its surroundings. These signalling cues ensure the correct activation of the Nodal signalling pathway and are subsequently transmitted to the LPM to guide organ primordia to their final position along the LR axis. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
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doctoralThesis |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/124504 http://hdl.handle.net/10803/650832 |
| url |
https://hdl.handle.net/2445/124504 http://hdl.handle.net/10803/650832 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd, (c) Pi, 2018 http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd, (c) Pi, 2018 http://creativecommons.org/licenses/by-nc-nd/3.0/ |
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openAccess |
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application/pdf |
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Universitat de Barcelona |
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Universitat de Barcelona |
| dc.source.none.fl_str_mv |
Tesis Doctorals - Departament - Genètica, Microbiologia i Estadística reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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1869403890534842368 |
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The role of the zebrafish tbx5 paralogues during eye, pectoral fin and heart development.Pi Roig, AinaPeix zebraMorfogènesiZebra danioMorphogenesis[eng] Tbx5 is a transcription factor expressed in the developing eyes, heart and upper limbs. Mutations in human TBX5 cause Holt-Oram syndrome (HOS), a condition characterised by heart and upper limb malformations. In zebrafish, a novel tbx5 gene (tbx5b), which emerged from the teleost specific genome duplication, is co-expressed with its paralogue (tbx5a). To understand tbx5 paralogues function and relationship in the different tissues where they are expressed (i.e. eye, heart and pectoral fin) in zebrafish, downregulation by morpholino oligonucleotides (MO) injection has been performed. The results reveal that tbx5 genes are essential for the development of these organs, where they have different requirements and relationships to ensure proper dorsoventral (DV) retina axis organization, the establishment of cardiac laterality and the induction and sustained outgrowth of the pectoral fin. In the retina, tbx5 genes role is redundant and both paralogues knock-down causes a reduction of the dorsal retina identity, concomitant with an expansion of the ventral retina markers expression, that results in defective DV patterning and subsequent thinner retinotectal projections. In contrast, tbx5a and tbx5b have gene-specific functions during pectoral fin development: tbx5a is required for the initiation of pectoral fin outgrowth, whereas tbx5b is later responsible for the sustained outgrowth of the pectoral fin. In the case of heart morphogenesis, both paralogues cooperate in the same pathway. In addition, our results uncover a novel role for tbx5 paralogues in the establishment of heart asymmetry in zebrafish embryos in both asymmetric events (i.e. cardiac jogging and looping) and an earlier role for tbx5a during the directional migration and of the cardiac precursors in the midline. Further analysis of the role of tbx5a during the establishment of left-right (LR) asymmetry shows that the expression of left-side markers from the Nodal signalling pathway expressed in the lateral plate mesoderm (LPM) is also randomized. Laterality defects during zebrafish development in tbx5a morphant are also found in neural and visceral laterality, suggesting an early role of tbx5a in LR establishment. Strikingly, tbx5a knock-down in the DFCs/KV (dorsal forerunner cells / Kupffer’s vesicle) lineage, the organ responsible for LR asymmetry generation, also results in cardiac jogging randomization. Furthermore, our results show an early tbx5a expression during gastrulation and an altered expression pattern for charon and a reduction on bmp4 expression levels around the KV at 10SS. In addition, a reduction on Bmp signalling levels in tbx5a DFC-specific morphants is detected, which is consistent with the identification of a putative binding site for Tbx5 that is conserved in high vertebrates for bmp2b and bmp4. Finally, the analysis of tbx5a morphants also show that they have a reduced KV. Overall, we propose a model in which tbx5 is required during zebrafish early development to achieve a proper KV size that will ensure a robust directional flow within the KV and Bmp signalling in the KV itself and its surroundings. These signalling cues ensure the correct activation of the Nodal signalling pathway and are subsequently transmitted to the LPM to guide organ primordia to their final position along the LR axis.[cat] Tbx5 és un factor de transcripció expressat durant el desenvolupament dels ulls, el cor les extremitats superiors. Mutacions en el TBX5 humà causa el síndrome de Holt-Oram, caracteritzat per malformacions al cor i en l’extremitat superior. En peix zebra, un nou gen tbx5 (tbx5b) va emergir de la duplicació específica del genoma dels teleostis i és co-expressat amb el seu paràleg (tbx5a). Per entendre la funció i la relació dels paràlegs de tbx5 en els diferents teixits on s’expressen (i.e. ull, cor i aleta pectoral) en peix ¬zebra, es va utilitzar la injecció de morfolinos per a reduir els nivells de tbx5. Els resultats revelen que els gens tbx5 són essencials pel desenvolupament d’aquests òrgans on hi tenen diferents requeriments i relacions per tal d’assegurar una correcta organització dorso-ventral (DV) a la retina, l’establiment de la lateralitat cardíaca i la inducció i creixement sostingut de l’aleta pectoral. En el cas del cor, els resultat revelen una nou rol per als paràlegs tbx5 en l’establiment de la lateralitat del cor en els embrions de peix zebra en ambdós esdeveniments asimètrics (jogging i looping). Els anàlisis del rol de tbx5a durant l’establiment de l’assimetria esquerra-dreta (LR) mostren que l’expressió dels marcadors del costat esquerra s’expressen de manera aleatòria en la placa mesodèrmica lateral (LPM) en els morfants per tbx5a i defectes en la lateralitat neural i visceral, suggerint un rol primerenc de tbx5a durant el desenvolupament. A més, la reducció de la mida de l’òrgan responsable de generar l’assimetria LR (KV: Kupffer’s Vesicle) en els morfants per tbx5a i la reducció en el nivell de senyalització de Bmps suggereixen que tbx5 és necessari durant el desenvolupament temprà del peix zebra per tal d’assegurar una mida adequada de la KV i una correcta senyalització al voltant de la KV, que després serà transmesa a la LPM per a guiar els primordis dels òrgans a la seva posició final al llarg de l’eix LR.Universitat de BarcelonaGarcia Fernández, JordiMinguillón Gil, CarolinaUniversitat de Barcelona. Departament de Genètica, Microbiologia i Estadística2018info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/124504http://hdl.handle.net/10803/650832Tesis Doctorals - Departament - Genètica, Microbiologia i Estadísticareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc-by-nc-nd, (c) Pi, 2018http://creativecommons.org/licenses/by-nc-nd/3.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1245042026-05-27T06:46:51Z |
| score |
15,300719 |