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

Abstract

Retinoic Acid (RA), a lipophilic molecule anda metabolite of Vitamin-A (all-trans-Retinol),is a well known morphogen that affects gene lranscription and modulales a wide variety of biological processes in vertebrales. The largets of all-trans-Retinoic Acid include a multilude of structural genes,oncogenes, transcription factors and cytokines.In this work we use a unique collection of zebrafish reporter lines generated in our l ab lo detect tissue specific downstream targels of RA. Here we present preliminary results suggesting lhat mycb, an oncogene whose misregulation has been relatad 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 lhe regulatory landscape of this gene. Another proyect in course is dealing wilh pancreatic cell differentiation. We are analyzing elements of the Salvador/Warts/Hippo pathway that seems lo be active during zebrafish pancreas development. The Hippo tumor suppressor palhway restricts organ size in Drosophila and mammals by antagonizing the oncoprotein Yki/YAP. Previous Chip-seq experiments for pancrealic transcription faclors suggest that the downstream targets of Hippo signaling pathway tead and yap could be importan!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 zebralish and that yap and tead play a crucial role in pancreas development by controlling cell proliferation and differenilation.