Cell lineage relationships in the development of the mammalian CNS: role of cell lineage in control of cerebellar Purkinje cell number.

This report continues our studies of the cell lineage relationships among the cells of the cerebellar Purkinje cell population. It examines the question of whether there are cell autonomous factors that regulate cell number during mammalian CNS development. Experimental aggregation chimeras were made by the joining of two embryos, one wild-type, one lurcher in genotype; both embryos were of C57BL/6 genetic background. Since all Purkinje cells of +/Lc genotype will degenerate, only wild-type Purkinje cells remain in the cerebellar cortex of the adult chimeras. The number of remaining cells does not vary uniformly from zero (the lurcher value) to wild-type (92,000 for C57BL/6). Rather the cells occur in numerical quanta that represent developmental clones of cells. In an earlier work, the Purkinje cell population of the C3H/HeJ inbred strain was shown to consist of eight such clones in each cerebellar half. Each C3H/HeJ clone contains 10,200 Purkinje cells. Evidence is presented in the present study that the Purkinje cells of the C57BL/6 strain, exist in 10 clones, of 9200 cells per half cerebellum. The findings suggest that a clonal organization exists in the Purkinje cell population of at least two inbred strains of mice, that differences in adult neuronal number can be due to either the number of clones present or the size of each individual clone (i.e., the number of cells per clone), and that the number of cells in a clone appears to be an autonomous property of the lineage itself and hence, presumably, of the progenitor cell that founded the clone.