Mitosis is a highly coordinated process that assures the fidelity of chromosome segregation. Errors in this process result in aneuploidy which can lead to cell death or oncogenesis. In this paper we describe a putative mammalian protein kinase, AIM-1 (Aurora and Ipl1-like midbody-associated protein), related to Drosophila Aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. AIM-1 message and protein accumulate at G 2 /M phase. The protein localizes at the equator of central spindles during late anaphase and at the midbody during telophase and cytokinesis. Overexpression of kinase-inactive AIM-1 disrupts cleavage furrow formation without affecting nuclear division. Furthermore, cytokinesis frequently fails, resulting in cell polyploidy and subsequent cell death. These results strongly suggest that AIM-1 is required for proper progression of cytokinesis in mammalian cells.

The generation cycle of germinative cells (external matrix cells) in the external granular layer of the cerebellar cortex of the 10-to l 1-day-old mouse was studied by radioautography following repeated injections of H3-thymidine. The generation time is 19 hr, presynthetlc time 8.5 hr, DNA-synthetic time 8 hr, postsynthetic time 2 hr, and mitotic time 0.5 hr. These proliferating cells occupy the outer half of the external granular layer and make up the external matrix layer. Neuroblasts are differentiated from the external matrix cell, migrate out from the layer and accumulate in the inner half of the external granular layer to form the external mantle layer. The transit time of the neuroblasts in the external mantle layer is 28 hr. Thereafter, they migrate farther into the molecular layer and the internal granular layer. By means of long-term cumulative labeling, the rate of daily production of neuroblasts from the external matrix cell is studied in quantitative terms. It becomes clear that the entire population of the inner granule neurons arises postnatally in the external granular layer between 1 and 18 days of age and that 95% of them is produced between postnatal days 4 and 15. Finally, the fate of the cells in the external granular layer at its terminal stage was studied by marking the cells with H3-thymidine during 15-16 days of life and following their subsequent migration and developmental changes up to 21 days of life. Comparison of radioautographs taken before and after the migration disclosed that the external matrix cells give rise to a small number of neuroglia cells. This finding revealed their multipotential nature.

Cell proliferation and migration in the external granular layer of the mouse cerebellum were studied with autoradiography after cumulative labeling with H3-thymidine. The germinative cells in the external granular layer were considered as externally dislocated matrix cells. Their generation time, presynthetic time, duration of DNA synthesis, postsynthetic time and mitotic time were determined in one-, three-, seven-and ten-day-old mice. The entire sequence of the ontogeny of the external granular cell-system was separated into three consecutive stages; stage 1 or stage of pure external matrix cell proliferation, stage 2 or stage of neuroblast production, and stage 3 or stage of neuroglia differentiation. Production of neuroblasts in the external granular layer at seven and ten days of life and their migration into the internal granular layer were demonstrated by means of autoradiography. Transit times of the neuroblasts migrating across the external mantle layer and the molecular layer of ten-day-old mice were estimated at 21 and four hours, respectively. More than 50% of the inner granular cells migrated from the external granular layer later than ten days of life and almost 81 to 92% were produced later than seven days of postnatal life. In conclusion, on the basis of the matrix cell concept, the authors tried to uniiy observations of previous and present investigators and presented a scheme of pre-and postnatal histogenesis of the mouse cerebellum.

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