title: Ontogenic regulation of spatial differentiation in the crypt-villus axis of normal and isografted small intestine.
abstract: Despite rapid proliferation, the mammalian intestinal epithelium maintains precise spatial differentiation from crypt to villus tip and from duodenum to colon. During perinatal life, the rodent gut undergoes a dramatic morphogenesis, resulting in formation of the crypt-villus and duodenal-colonic axes. The ontogeny of regional differences in gene expression in the emerging vertical axis has not been well described. We used the liver fatty acid binding protein (L-FABP) and apolipoprotein (apo) AIV genes as markers of neonatal enterocytic differentiation. In situ hybridization analyses revealed that both genes exhibit unique spatial patterns of expression along the jejunal crypt-villus axis during ontogeny, characterized by increased cellular mRNA levels in villus base enterocytes. To examine the requirement for a normal luminal environment to generate these precise patterns of cellular gene expression, we employed intestinal isograft techniques. Fetal intestines were implanted as early as embryonic day 12. Appropriate expression of the apo AIV and L-FABP genes was recapitulated during villus morphogenesis in fetal life. However, spatial patterns of gene expression in the isografted postnatal cryptvillus axis were altered. The preferential accumulation of L-FABP and apo AIV mRNA in villus base enterocytes was never observed in isografts. These results suggest that a "basal" differentiation program is encoded in fetal endoderm and mesenchyme, yet extracellular substances contained in the lumen or extrinsic to the intestine play an important modulatory role in generating spatial differentiation during ontogeny.
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D016332:Fetal Tissue Transplantation; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000166:cytology / Q000254:growth & development* / Q000637:transplantation*; D008871:Microvilli / Q000378:metabolism; D018996:Myelin P2 Protein / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012177:Retinol-Binding Proteins / Q000378:metabolism; D054840:Retinol-Binding Proteins, Cellular; D014185:Transplantation, Isogeneic
chemical_list: D001054:Apolipoproteins A; D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C518460:Rbp2 protein, mouse; C518461:Rbp2 protein, rat; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; C022205:apolipoprotein A-IV