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Title page for ETD etd-03062006-135146


Type of Document Dissertation
Author Cha, Yong I.
Author's Email Address yong.cha@vanderbilt.edu
URN etd-03062006-135146
Title Cyclooxygenase-1 derived prostaglandin E2 (PGE2) signaling in early development
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Susan R. Wente Committee Chair
Chin Chiang Committee Member
Lawrence J. Marnett Committee Member
Lilianna Solnica-Krezel Committee Member
Raymond N. DuBois Committee Member
Sudhansu K. Dey Committee Member
Keywords
  • cellular control mechanisms
  • development
  • cyclooxygenase
  • prostaglandin
  • zebrafish
  • cancer
Date of Defense 2006-01-25
Availability unrestricted
Abstract
Prostaglandin G/H synthases (PGHS), commonly referred to as cyclooxygenases (COX-1 and COX-2), catalyze a key step in the synthesis of biologically active prostaglandins (PGs), the conversion of arachidonic acid (AA) into prostaglandin H2 (PGH2). PGs have important functions in a variety of physiologic and pathologic settings, including inflammation, cardiovascular homeostasis, reproduction, and carcinogenesis. However an evaluation of prostaglandin function in early mammalian development has been difficult due to the maternal contribution of prostaglandins from the uterus. The emergence of zebrafish as a model system has begun to provide some insights into the roles of this signaling cascade during vertebrate development. In zebrafish, COX-1 derived prostaglandins are required for two distinct stages of development, namely during gastrulation and segmentation. During gastrulation, PGE2 signaling promotes cell motility, without altering the cell shape or directional migration of gastrulating mesodermal cells via the G-protein coupled prostaglandin E2 receptor (EP4). During segmentation, COX-1 signaling is also required for posterior mesoderm development, including the formation of vascular tube structures, angiogenesis of intersomitic vessels, and pronephros morphogenesis. We propose that deciphering the role for prostaglandin signaling in zebrafish development could delineate mechanistic details underlying various disease processes that result from perturbation of this pathway and uncover novel potential therapeutic targets.
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