DYNAMICS OF EPITHELIAL-CELLS IN THE CORPUS OF THE MOUSE STOMACH .4. BIDIRECTIONAL MIGRATION OF PARIETAL-CELLS ENDING IN THEIR GRADUAL DEGENERATION AND LOSS

The life story of parietal cells has been investigated in the corpus of the mouse stomach using electron microscopy and H-3-thymidine radioautography. Parietal cells are scattered in the four regions of the unit. On the average 3.6 cells are in the pit, 6.2 in the isthmus, 5.6 in the neck, and 10.6 in the base. Parietal cells do not divide. They arise from partially differentiated pre-parietal cells, which are believed to be derived in the isthmus from the three subtypes of granule-free cells: undifferentiated cells, pre-pit cell precursors, and pre-neck cell precursors. Radioautography indicates that the transformation of granule-free cells into pre-parietal cells takes at least one day. The pre-parietal cells, of which there are 0.6 per unit on the average, develop into parietal cells through three successive stages. Stage 1 is characterized by small immature cells that are identified by long apical microvilli. Stage 2 is characterized by larger cells, about one-third the size of parietal cells, and by an incipient canaliculus and a few apical tubulovesicles. Stage 3 is characterized by the expansion of the canalicular and tubulovesicular systems as well as mitochondrial enlargement, which cause the pre-parietal cell to gradually approach the size of, and eventually become, a parietal cell. This cell sequence mainly takes place in the isthmus, but may extend to the neck region. Continuous infusion of H-3-thymidine confirms that parietal cells originate in the isthmus and that they migrate in two directions: some go outward to the pit and the others migrate inward to the neck and eventually to the base. It has been estimated that for every six parietal cells produced per month in the isthmus, three migrate to the pit and three migrate to the neck to eventually reach the base. While almost all parietal cells in the isthmus and neck appear normal, a large proportion of those reaching the pit (21%) and base (23%) undergo gradual alteration and degeneration. After the ensuing death, parietal cells are eliminated in one of two major ways: 1) extrusion into the gastric lumen, if they appear necrotic, or 2) phagocytosis by a neighboring cell or even by an invading connective tissue macrophage, if they are apoptotic. The overall turnover time of parietal cells averages 54 days. Briefly, a sequence of cells-the parietal cell lineage-is initiated in the isthmus, where the three subtypes of granule-free cells are presumed to give rise to pre-parietal cells, which then differentiate into parietal cells. Half of the parietal cells migrate away in the direction of the gastric lumen and gradually degenerate as they approach the free surface, while the other half migrate in the other direction toward the unit's blind end, where they degenerate and are eliminated.