Deciphering the role of alternatively spliced microexons during vertebrate nervous system development and function

• Autores: Laura López Blanch
• Directores de la Tesis: Manuel Irimia (dir. tes.)
• Lectura: En la Universitat Pompeu Fabra ( España ) en 2021
• Idioma: español
• Tribunal Calificador de la Tesis: Cristina Pujades Corbi (presid.), Jonás Juan Mateu (secret.), Gaia Gestri (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
• Materias:
  • Ciencias de la vida
    • Biología animal (zoología)
      • Comportamiento animal
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Neural microexons are the most conserved type of alternative splicing, suggesting a strong functional relevance. Consistently, mutation of their master regulators leads to dramatic neurodevelopmental alterations and autistic-like behaviors. However, the functional relevance of individual microexons has only been elucidated for a few cases. Here, I aimed at investigating the roles of individual microexons using zebrafish as a model system. We selected 18 microexons conserved from fish to humans and generated deletion lines using CRISPR-Cas9. None of these deletions produced gross phenotypic alterations or affected viability and fertility. However, a finer characterization using different tests I have developed or adapted during my PhD revealed a wide range of phenotypes at the cellular, tissular, behavioral and/or molecular level. Interestingly, in many cases, these phenotypes were in opposite directions, a pattern that was mirrored at the transcriptomic level. Altogether, our results depict a rich scenario for the functionality of microexons.