The Regulation of Delta-like 4 in Thymic Epithelial Cells as a Model for Organ Structure Affecting Gene Regulation

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The thymus is the primary site responsible for the production of T cells from bone marrow-derived lymphocyte progenitors. Key to this function is the expression of the Delta-like 4 (Dll4) gene product on the surface of thymic epithelial cells (TECs). Despite playing an indispensable role in T-cell development, the molecular factors controlling the expression of Dll4 remain largely unexplored. While we know that the TECs must be maintained in a 3-dimensional (3D) structure to successfully express Dll4, we do not know why that is nor what molecules connect 3D structure to Dll4 expression. Our work aims to understand the link between the 3D thymic microenvironment and correct gene expression in TECs. In doing so, we will gain a better understanding of how the thymus functions. We also feel that our work will result in the discovery of shared pathways between TECs and other cell types requiring 3D structure to properly function (i.e. hepatocytes, and mammary epithelial cells). This understanding will provide valuable information and lay the foundation for research into improving methods for tissue regeneration and bioengineering.