The adult intestine contains a rapidly proliferating and differentiating epithelium. In the seven days prior to birth, the proliferating and differentiating epithelium. In the seven days prior to birth, the rodent small intestinal epithelium undergoes remarkable proliferation and morphological differentiation. Little is known about the molecular and cellular basis of fetal epithelial differentiation. Factors which are hypothesized to influence epithelial differentiation include diet, pancreaticobiliary secretions and hormones. A recent study (Rubin et al., App. B) has shown that the fatty acid binding proteins (FABPs) and apolipoproteins (apo) AI and AIV are sensitive markers of the complex patterns of epithelial differentiation which occur during late fetal life in the rodent. This proposal seeks to i. examine transcriptional activation of the FABP and apo AI and AIV genes in the fetal intestinal epithelium using in situ hybridization, ii. provide novel molecular markers needed to study epithelial differentiation during this critical period of gut development by isolating genes from fetal intestinal cDNA libraries, using probes enriched by """"""""subtractive"""""""" hybridization, and iii. examine the influence of gut environmental factors on epithelial differentiation by analyzing gene expression in fetal intestinal isografts implanted in syngeneic hosts. The FABP and apo AI and AIV genes will be used as markers of differentiation. RNA dot blot, in situ hybridization and immunocytochemical techniques will be used.
