Evolutionary recruitment and assembly of embryonic alternative splicing programs
[eng] In the present work, we studied the evolution of alternative splicing (AS) from different perspectives. First, we performed a preliminary analysis where we identified alternative exons with tissue-specific regulation in five species of deuterostomes: Homo sapiens, Danio rerio, Callorhinchus mi...
| Autor: | |
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/117684 |
| Acceso en línea: | https://hdl.handle.net/2445/117684 http://hdl.handle.net/10803/456241 |
| Access Level: | acceso abierto |
| Palabra clave: | Regulació genètica Genètica Proteïnes Biologia molecular Genetic regulation Genetics Proteins Molecular biology |
| Sumario: | [eng] In the present work, we studied the evolution of alternative splicing (AS) from different perspectives. First, we performed a preliminary analysis where we identified alternative exons with tissue-specific regulation in five species of deuterostomes: Homo sapiens, Danio rerio, Callorhinchus milii, Branchiostoma lanceolatum and Strongylocentrotus purpuratus. Seven different organs from each animal were employed, trying to use homologous tissues when possible (especially among vertebrates). Results revealed a higher relative proportion of organ-biased AS regulation in the nervous system of chordates, with respect to the rest of organs. From the other hand, sea urchin species showed more balanced amounts of organ-specific AS regulation. Moreover, human samples showed a tissue-specific trend towards increased levels of differential exon skipping in general. In this thesis, we also investigated the expression and function of RbFox and Nova genes in non-vertebrate deuterostome organisms to study the evolutionary scenario of both families. The two gene families code for RNA-binding proteins that regulate wide sets of alternative splicing events in vertebrate organisms. We found Nova function to be related to gastrulation movements during embryogenesis, but not endoderm specification. In all adult Bilateria organisms studied, RbFox genes are strongly expressed in the nervous system. But, strikingly, non-vertebrate deuterostomes present developmental expression in mesoderm tissues, especially in the myogenic lineage. Interestingly, RbFox activity has been co-opted in the central nervous system of bony vertebrates, as well as in the skeletogenic mesoderm of S. purpuratus. In this last species, RbFox is necessary for both the formation of circumesophageal muscles and the development of the larva skeleton. At the splicing level, Nova ortholog in sea urchin regulates splicing of a very vast set of exons, while the number of RbFox-dependent exons is much lower. Among the targets of the latter, we detected the Fgfr1 gene, that have been previously described as necessary in terms of muscle differentiation in this organism. Finally, we studied Esrp gene family, which codes also for a splicing factor. We investigated the expression and function of this gene family in several species of deuterostomes. In zebrafish, Esrp1 and Esrp2, are involved in the organogenesis of multiple structures, arguably by controlling epithelial-mesenchymal interactions. In Ciona intestinalis, Esrp ectopic expression is able to modulate the motility of mesenchymal migratory cells. In amphioxus, Esrp is expressed in the precursor of the epidermic sensory neurons at the time they ingress in the dorsal ectoderm. In S. purpuratus, Esrp is found in both aboral ectoderm and in the pigment cells during gastrulation. In fact, the gene is needed for a complete integration of those cells in the non-neural ectoderm. We detected multiple regulated exons that are shared among bony vertebrate organisms in terms of Esrp-regulated splicing, and we even found a case conserved also in amphioxus in Fgfr genes. However, no regulated exons have been detected as conserved between vertebrates and sea urchin, although several common targets are found at the gene level. |
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