Análisis genómicos y funcionales para determinar el papel de protooncogenes en el desarrollo embrionario de vertebrados

• Autores: Mario Luengo Díaz
• Directores de la Tesis: Andrés Garzón (dir. tes.), José Luis Gómez Skarmeta (dir. tes.)
• Lectura: En la Universidad Pablo de Olavide ( España ) en 2014
• Idioma: español
• Tribunal Calificador de la Tesis: Juan Ramón Martínez Morales (presid.), José Luis Royo Sánchez-Palencia (secret.), Beatriz Estrada Martín (voc.)
• Materias:
  • Química
    • Bioquímica
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: RIO
• Resumen

  • Retinoic Acid (RA), a lipophilic molecule and a metabolite of Vitamin-A (all-trans-Retinol), is a well known morphogen that affects gene transcription and modulates a wide variety of biological processes in vertebrates. The targets of all-trans-Retinoic Acid include a multitude of structural genes, oncogenes, transcription factors and cytokines. In this work we use a unique collection of zebrafish reporter lines generated in our lab to detect tissue specific downstream targets of RA. Here we present preliminary results suggesting that mycb, an oncogene whose misregulation has been related to different types of cancers, is repressed specifically in the branchial arches by RA, situation that leads to a decrease in cell proliferation. In addition, we are analyzing the genomic landscape of this gene using Circularized Chromosome Conformation Capture (4C). By this way we will identify genome wide DNA sequences that interact with the promoter of mycb which might correspond to elements of the regulatory landscape of this gene. Another proyect in course is dealing with pancreatic cell differentiation. We are analyzing elements of the Salvador/Warts/Hippo pathway that seems to be active during zebrafish pancreas development. The Hippo tumor suppressor pathway restricts organ size in Drosophila and mammals by antagonizing the oncoprotein Yki/YAP. Previous Chip-seq experiments for pancreatic transcription factors suggest that the downstream targets of Hippo signaling pathway tead and yap could be important for a proper expression of developmental genes in pancreas. In this work we show preliminary results from the manipulation of the Hippo signaling pathway suggesting that it is active also in zebrafish and that yap and tead play a crucial role in pancreas development by controlling cell proliferation and differentiation.