GASTRIC EPITHELIAL MORPHOGENESIS IN NORMAL AND TRANSGENIC MICE

The epithelium located in the corpus of the adult mouse stomach farms mucosal invaginations known as gastric units. Gastric units are popula ted by members of the pit, parietal, and neck-zymogenic cell lineages, all of which are derived from multipotent stem cells. Gastric unit mo rphogenesis was examined in normal embryonic day 18 (E18) to postnatal day 28 (P28) FVB/N mice with electron microscopy and multilabel immun ohistochemistry. E18 units appear as short, solid infoldings (primordi al buds), 92% of whose cells represent pit, parietal, and neck cell pr ecursors. Although the total number of cells per bud does not change f rom P1 to P7, immature cells decrease to 22% as differentiated pit, ne ck, and parietal cells appear. From P7 to P15, lineage precursors and their differentiated progeny increase and buds elongate. Between P15 a nd P21 the multipotent stem cell and its descendants are assembled int o a distinct proliferative zone (isthmus) located in the midportion of each unit, and cellular migration-differentiation programs become com partmentalized. To examine the role of parietal cells in regulating ga stric unit morphogenesis, nucleotides -1035 to +24 of the mouse H+-K+- adenosinetriphosphatase beta-subunit gene were used to express simian virus 40 large T antigen (SV40 TAg) exclusively in this lineage. SV40 TAg amplified the normally rare pre-parietal cell and disclosed a pre- parietal cell precursor. Pre-parietal cells and their precursors were the predominant cells in E18-P1 transgenic buds. At later stages of de velopment (P1-P28) there was a block in differentiation of pre-parieta l to mature parietal cells, a decrease in neck cells, and a marked dep letion of zymogenic cells. These findings suggest that members of the parietal cell lineage are the source of instructions that affect the n eck-zymogenic cell lineage, even before the gastric unit is compartmen talized into its anatomically distinct pit, isthmus, neck, and base re gions.