Non-apoptotic expression of active caspase-3 during rat cerebellar development

Caspases are cysteine proteases that mediate stereotypical dismantling of the cell that results in characteristic morphological modifications termed apoptosis. There are 14 known mammalian caspases, out of which the key downstream effector in the execution of apoptosis is active/cleaved caspase- 3. Apart from its role in mediating apoptosis, in recent years caspase-3 activation has been shown to induce differentiation of certain cell types. The hypothesis underlying these studies is: Non-apoptotic expression of active/cleaved caspase-3 is instrumental for cellular differentiation in the developing rat cerebellum. The following aims were addressed to test this hypothesis: 1) To demonstrate the expression of active caspase-3 in cells of developing cerebellar cortex; 2) To identify the developmental phenotype of active caspase-3 expressing cells; 3) To establish that active caspase-3 expression is not linked to an apoptotic event; 4) To develop and characterize an enriched Bergmann glia culture; 5) To assess the expression of active caspase-3 in cultured Bergmann glia; 6) To identify the developmental phenotype of active caspase-3 expressing cells; and 8) To establish the functional consequences of active caspase-3 inhibition on the developmental state of Bergmann glia. Findings from these studies suggest that caspase-3 participates in the differentiation of both granule cells and Bergmann glia and it functions in a highly tissue or cell type -dependent way. These data strongly suggest a role of active/cleaved caspase-3 in granule cell and glial developmental physiology.