Overview
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Dan A. Wiginton, PhD
Developmental Biology Division, ML 7007
Cincinnati Children's Research Foundation
3333 Burnet Avenue
Cincinnati, OH 45229-3039
Phone: (513) 636-4547
Fax: (513) 636-4317
dan.wiginton@cchmc.org |
The Wiginton laboratory investigates 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.
It is proposed that a discrete network of regulatory factors control these processes. Profiles of expression exist along the crypt-villus axis that are dependent on cell type, differentiation status, and cell migration. In addition, significant variations in gene expression are observed along the cephalocaudal (horizontal) axis of the intestine. These functional variations are established and maintained in the adult even though the intestinal epithelium undergoes a constant, continuous renewal.
There are also significant changes in gene expression specifically associated with intestinal development during fetal and early post-natal stages. The adenosine deaminase gene is currently being used as a model to begin to understand the interrelated network of transcription factors and cis-acting elements that specify these genetic programs and regulate gene expression along the various physical and temporal axes of the small intestine in humans and mice. Specific roles and functions have been defined for the regulatory transcription factors Pdx-1 and the GATA family of GATA-4, -5, and -6. Pdx-1 has a critical role in intestinal gene regulation along the cephalocaudal axis. Preliminary studies indicate that the GATA factors may be key regulators controlling cell fate determination and cellular differentiation from the intestinal stem cell.
