DYNAMICS OF EPITHELIAL-CELLS IN THE CORPUS OF THE MOUSE STOMACH .3. INWARD MIGRATION OF NECK CELLS FOLLOWED BY PROGRESSIVE TRANSFORMATION INTO ZYMOGENIC CELLS

The neck cells (or mucous neck cells) present in the neck region and t he zymogenic cells (or chief cells) present in the base region of the units in the mouse corpus were examined in the electron microscope (EM ) and in radioautographs prepared after administration of H-3-thymidin e by single or multiple injections or by continuous infusion for 1-52 days. For these studies, the neck region of the units has been subdivi ded into three equal segments, respectively named high neck, mid neck, and low neck, while the base region has been similarly subdivided int o high base, mid base, and low base. The neck region includes an avera ge of 12.6 neck cells, characterized in the EM by dark, mucous secreto ry granules that frequently exhibit a light, pepsinogenic core. Contin uous H-3-thymidine infusion reveals that neck cells come from pre-neck cells, which are believed to arise in the isthmus region from the und ifferentiated granule-free cells through a pre-neck cell precursor sta ge. The pre-neck cells, characterized by the presence of a few cored s ecretory granules, migrate inward (i.e., in the direction of the blind end of the units) and enter the neck region to become neck cells. It is estimated that 59% of the neck cells arise from differentiation of pre-neck cells, whereas the other 41% are derived from their own mitos es. Neck cells migrate inward in 1-2 weeks from the high through the m id and low neck segments, while they keep on producing more and larger secretory granules and thus further differentiate as mucus-producing cells. When neck cells reach the high base segment, they become pre-zy mogenic cells that produce secretory granules in which appear light, i rregular, pepsinogenic patches which encroach on the dark mucous conte nt. With time, the pre-zymogenic cells, of which there are 5.0 per uni t on the average, keep on producing new granules with larger and large r light patches, so that in the end the cells produce granules which a re entirely filled by light, pepsinogenic material. At this stage, the cells are zymogenic cells. Zymogenic cells, which average 67.5 per un it, further migrate inward, while gradually enlarging and producing pe psinogenic granules of increasing size. In the low base segment, some zymogenic cells show signs of degeneration leading to death by either necrosis or apoptosis. While remnants of the necrotic cells appear to be released to the unit lumen, the apoptotic cells are phagocytosed by a neighboring zymogenic cell or by a connective tissue macrophage bre aking through the basement membrane of the oxyntic unit. Briefly, the zymogenic cell lineage, a cell sequence initiated from the stationary undifferentiated granule-free cells, includes pre-neck cell precursors , pre-neck cells, neck cells, pre-zymogenic cells, and finally zymogen ic cells, which all migrate in the direction of the unit's blind end, near which zymogenic cells are lost.