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Title page for ETD etd-01252012-155505

Type of Document Dissertation
Author Cross, Emily Elizabeth
URN etd-01252012-155505
Title Studies on the Molecular Regulation of Epicardial Cell Movement
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
H. Scott Baldwin Committee Chair
Alissa Weaver Committee Member
David Bader Committee Member
Matthew Tyska Committee Member
Sandra Zinkel Committee Member
  • Small Organic Molecules
  • NDRG4
  • Bves
  • migration
  • cell biology
  • heart
Date of Defense 2012-01-20
Availability unrestricted
Epicardial development is a complex process that involves tightly regulated coordination of concurrent cellular behaviors ranging from sheet migration to secretion. The regulation of these behaviors is poorly understood, and epicardial cell biological studies will improve the understanding of heart development and subsequent function. Here, a novel small organic molecule screening methodology of epicardial behaviors is used to elucidate regulatory relationships governing this developmental program. As proof-of-principle, a novel signaling relationship was identified in which TGFβ and BMP signal cascades cooperatively regulate epicardial sheet migration. It is further demonstrated here that epicardial cells participate in a newly identified cellular behavior: regulated cell movement through autocrine extracellular matrix (ECM) deposition. The studies identify two novel regulators of autocrine ECM deposition, Bves and NDRG4. Additionally, we demonstrate that Bves regulates cell surface trafficking of the focal adhesion component β1-integrin through an interaction with VAMP3, a v-SNARE recycling endosome component. These studies in combination with previous work indicate that Bves functions in epicardial cells and globally to traffic adhesion components to the cell surface. This positions Bves as a general regulator of cell-cell and cell-matrix adhesion. Taken together, these studies elucidate regulation of epicardial cell behaviors, reveal a novel epicardial behavior, and suggest a global mechanism for Bves diverse effects of development and disease.
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