Spatial analysis of transcriptional activation in fetal rat jejunal and ileal gut epithelium

In the week before birth (days 15-21 of the 22-day gestation period), the fetal rat small intestinal epithelium undergoes rapid proliferation and differentiation. The developing gut changes from a mesenchymal tube lined by endoderm to a complex absorptive surface composed of differentiated epithelium overlying nascent villi. To begin to characterize the molecular events that take place in nascent intestinal epithelial cells as cytodifferentiation proceeds from jejunum to ileum, we examined spatial, temporal, and cellular patterns of transcriptional activation of the rat liver fatty acid-binding protein (L-FABP) and apolipoprotein (apo) AIV genes. In situ hybridization analyses revealed that transcription of both genes is activated in the jejunum between fetal days 17 and 18, yet their expression is not initiated in the ileum until 1-2 days later. Transcriptional activation proceeds in a "wavelike" fashion along the horizontal length of the gut and coincides with villus morphogenesis. As nascent villi emerge, heterogeneous cellular accumulation of L-FABP mRNA occurs in both fetal jejunal and ileal epithelium, but persists only in the ileum. In contrast, cellular expression of apo AIV mRNA in nascent epithelium is predominantly homogeneous in both regions of the gut. These results indicate that transcriptional activation in the fetal gut epithelium is a complex, dynamic process that is spatially regulated along the horizontal axis of the intestine. Initiation of transcription in enterocytes is closely linked to villus morphogenesis and histological cytodifferentiation.