Cell lineage analysis of cerebellar Purkinje cells in mouse chimeras

Murine chimeras provide an experimental system in which cell lineage analysis of the mammalian central nervous system (CNS) can be accomplished. Utilizing a cell marker system that permits the identification of cells of each genotype in various cell populations present in histologic sections of the CNS at different developmental periods, fate maps of the mammalian CNS can be constructed. Thus, the presence or persistence of clones of cells can be readily visualized in simply organized CNS regions, like the cerebellar cortex. The electrophoretic variants of the glycolytic enzyme, glucosephosphate isomerase (GPI, E.C. 5.3.1.9; GPI-1A, GPI-1B), are the genotype-specific cell markers most commonly used by experimental mammalian embryologists in studies of cell lineage utilizing mammalian chimeras. We have adapted this cell marker system to permit the visualization and unequivocal identification of cells containing the GPI-1B variant throughout the CNS of adult BALB cBy^J a3 C57BL 6J chimeric mice. Utilizing allozyme-specific anti-GPI-1B antisera in immunocytochemical (PAP) staining techniques, we can score small as well as large cell populations, neurons as well as glia. We have reconstructed and statistically analyzed the location and distribution of chimerism present in the Purkinje cell population of four of these chimeric mice. We found the Purkinje cells in each of these animals existed as small (3-8) cell patches of like genotype that were not randomly arranged. This suggests that clones of cells may persist as contiguous groups of cells throughout mammalian cerebellar development.