The research in Dan Wiginton’s lab is devoted to the use of transgenic and gene knockout mouse models to investigate in vivo mechanisms of gene regulation during cell differentiation and tissue (or organ) development.
Research in the Wiginton Lab currently focuses on in vivo mechanisms of gene regulation controlling development of the small intestine and cell differentiation along the crypt-villus axis of the small intestinal epithelium. Epithelial cells differentiate, from stem cells localized in the crypt, into four major functional cell types (enterocytes, goblet cells, Paneth cells and enteroendocrine cells). It is proposed that a discrete network of regulatory factors control these biological processes, and the Wiginton Lab is attempting to understand the role of various factors in this network. In addition, Wiginton’s lab is investigating the genetic programs that regulate profiles of gene expression along the various physical and temporal axes of the small intestine.
Significant variations in gene expression are observed along the cephalocaudal (horizontal) axis of the intestine within a particular cell type. These functional variations are established and maintained in the adult even though the intestinal epithelium undergoes a constant, continuous renewal. Changes in gene expression are also observed along the intestinal crypt-villus axis, related to cell differentiation status and cell migration. There are also very significant temporal changes in gene expression during fetal and early postnatal stages of intestinal development. Little is understood about how these temporal changes are orchestrated and regulated. Recent work in Wiginton’s lab indicates that Onecut factors (OC-2 and OC-3) play an important role in temporal regulation in the intestinal epithelium. These studies promise to reveal much about the mechanisms by which digestive function is established in the small intestine.