Microarray Techniques Used to Identify Genes Controlling the Development of the Mouse Gastrointestinal Tract

Bruce J. Aronow
University of Cincinnati College of Medicine
R01ES08822

Background: Understanding the molecular basis of gene expression along the anterior-posterior (A-P) axis of the mammalian gastrointestinal (GI) tract is a critical need for determining the genes that are involved in the embryonic development of the GI tract, how gene expression occurs, and how development progresses. This understanding has been lacking, but using novel microarray gene expression techniques can lead to rapid discovery of candidate genes responsible for GI development along the length of the GI tract.

Advance: This team of investigators hypothesized that patterns of gene expression along the A-P axis could be defined at the gene and molecular level by analyzing expression profiles of large numbers of genes. Microarrays containing over 8,600 complementary DNA (cDNA) sequences were used to define expression profiles for mouse stomach, duodenum, jejunum, ileum, cecum, proximal colon, and distal colon. Highly expressed cDNAs were classified based on segmental expression patterns and protein function. The investigators found 571 cDNAs which were expressed at least 2-fold higher than reference in at least one GI region. Most of the genes displayed sharp boundaries at anatomically defined locations. Boundaries were especially sharp for genes encoding proteins that function in intermediary metabolism, transport, and cell-cell communicationfunctions critical for the proper coordination of GI function. Genes with distinct expression profiles were compared with mouse and human genomic sequence for promoter analysis and gene discovery.

Implications: The anatomically defined regions of the GI tract can also be defined by the pattern of expression profiles from genes located in and controlling functions in these regions. Distinctions in gene expression patterns between the small and large intestines were much less striking than those between the stomach and the small and large intestines. The investigators also identified new genes not previously known to be expressed in GI tissue. Identification of genes co-regulated along the A-P axis provides a basis for new insights, research, and gene discovery relevant to GI development, differentiation, function, disease, and therapeutic interventions.

Citation: Bates MD, Erwin CR, Sanford LP, Wiginton D, Bezerra JA, Schatzman LC, Jegga AG, Ley-Ebert C, Williams SS, Steinbrecher KA, Warner BW, Cohen MB, and Aronow BJ. Novel genes and functional relationships in the adult mouse gastrointestinal tract identified by microarray analysis. Gastroenterology 2002;122:1467-1482.