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Title page for ETD etd-09082009-142505


Type of Document Dissertation
Author Speirs, Christina Koo Yang
URN etd-09082009-142505
Title Prostaglandin Gbetagamma signaling stimulates gastrulation movements by limiting cell adhesion through Snail stabilization
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
James G. Patton Committee Chair
Bruce Appel Committee Member
Douglas P. Mortlock Committee Member
Joshua T. Gamse Committee Member
Lilianna Solnica-Krezel Committee Member
Keywords
  • development
  • cell motility
  • protrusion formation
  • E-cadherin
Date of Defense 2009-08-20
Availability unrestricted
Abstract
Prostaglandin E2 (PGE2) influences many processes in vertebrates, including development, homeostasis, and disease through its GPCRs EP receptors 1-4. PGE2 regulates gastrulation movements during zebrafish embryogenesis, but how it does so was previously unclear, as PGE2 can affect cell adhesion, motility, proliferation, and survival. Our studies reveal that the loss of PGE2 synthesis impairs all gastrulation movements, epiboly, internalization, convergence, and extension, in part due to increased cell adhesion in the embryo. The increase of tight junctions (ZO1) and adherens junctions (E-cadherin) occurs in a germ layer-dependent fashion. In the mesendoderm, PGE2 modulates E-cadherin by stabilizing Snail through the inhibition of Gsk3β by a novel interaction with the Gβγ subunits (in collaboration with K. Jernigan and E. Lee). Moreover, the reduction of PGE2 synthesis results in an endoderm deficiency without significant effect on the mesoderm, possibly due to decreased Nodal signaling. Finally, we present preliminary characterization of a fish harboring a reverse genetics TILLING-generated ep4a nonsense mutation that strongly depletes function of the gene, but manifests no apparent phenotype. In conclusion, our findings suggest that PGE2 signaling can coordinate cell fate specification and movement, in part through its negative regulation of cell adhesion in zebrafish gastrulae.
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