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 o f the mouse stomach using electron microscopy and H-3-thymidine radioa utography. Parietal cells are scattered in the four regions of the uni t. 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 ar ise from partially differentiated pre-parietal cells, which are believ ed to be derived in the isthmus from the three subtypes of granule-fre e 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. Th e pre-parietal cells, of which there are 0.6 per unit on the average, develop into parietal cells through three successive stages. Stage 1 i s characterized by small immature cells that are identified by long ap ical microvilli. Stage 2 is characterized by larger cells, about one-t hird 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 mitochondria l enlargement, which cause the pre-parietal cell to gradually approach the size of, and eventually become, a parietal cell. This cell sequen ce mainly takes place in the isthmus, but may extend to the neck regio n. Continuous infusion of H-3-thymidine confirms that parietal cells o riginate 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 ev entually to the base. It has been estimated that for every six parieta l cells produced per month in the isthmus, three migrate to the pit an d three migrate to the neck to eventually reach the base. While almost all parietal cells in the isthmus and neck appear normal, a large pro portion 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 c ell or even by an invading connective tissue macrophage, if they are a poptotic. 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 pre sumed to give rise to pre-parietal cells, which then differentiate int o parietal cells. Half of the parietal cells migrate away in the direc tion of the gastric lumen and gradually degenerate as they approach th e free surface, while the other half migrate in the other direction to ward the unit's blind end, where they degenerate and are eliminated.