Thesis: Juliana GUTIERREZ
Mar 28, 2014
from 02:00 to 05:00
|Salle des Thèses
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28th of March, in Thesis Room (ENS, Monod campus) Juliana Gutierrez Mazariegos from Vincent Laudet's team will defend her thesis entitled:
"Evolution of the retinoic acid receptor"
Retinoic acid (RA) is a fat-soluble morphogen derived from vitamin A that controls key cellular and developmental processes in chordates. In vertebrates, the major actors of the RA signaling pathway are the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are members of the nuclear receptor superfamily. These receptors activate transcription in the presence of their ligand, RA. The evolution of RAR is still poorly understood as it has been studied in detail only in vertebrate and some chordate species. Recently, RARs have been identified in the genome of non-chordate species, suggesting that RAR and the RA pathway might have a more ancient evolutionary origin than previously thought. The work presented in this manuscript allowed us to retrace the evolutionary history of RAR from its origin in Urbilateria, the last common ancestor of all bilaterians, to its diversification following whole genome duplication events in vertebrates. We describe the molecular characterization of the RARs from an annelid, a mollusk and a sea urchin. We showed that the receptors from the annelid and the sea urchin are functional RARs, however, the receptor from the mollusk is not functional with RA. Transcriptomic studies carried out in the annelid, Platynereis dumerillii revealed that the signaling pathways regulated by RA in this species are different to the ones it regulates in vertebrates. These observations along with the absence of RA binding by the mollusk RAR raise questions about the function of RA and RAR on the embryonic development of non-chordate species and their possible function in Urbilateria. Finally, the molecular characterization of cyclostome RARs allowed us to characterize the impact of whole genome duplications on the evolution of the ligand-binding pocket as well as reconstructing the ligand-binding pocket of the vertebrate ancestral RAR. Altogether, these data will allow us to better understand the relationship between the receptor and its ligand and to reveal novel insights on the function of RAR in response to non-classical ligands.