Key apoptosis regulating proteins are down-regulated during postnatal tissue development

The intrinsic apoptotic pathway is essential for murine development. We have previously shown that key mediators of this pathway, such as Bim, Apaf-1 and caspase-3, are down-regulated during the postnatal development of the retina. In this study, we demonstrate that this expression pattern is a feature of other distinct tissues such as the brain, heart and skeletal muscle. Caspase-9 expression is also examined and is shown to follow a different pattern in each tissue. Interestingly, we show that peripheral cells of the internal granular layer of the cerebellum do not down-regulate the intrinsic apoptotic pathway proteins Bim, Apaf-1 or caspase-3. Furthermore, Bim expression is also detectable in the brain stem and the CA3 region of the hippocampus in the adult cerebrum. Finally, we demonstrate that the incidence of TUNEL positive cells in the selected tissues decreases during postnatal development in correlation with the general down-regulation of key apoptotic pathway proteins. In contrast, we also demonstrate that apoptosis persists in the adult thymus and that this tissue continues to express Bim, Apaf-1 and caspase-3 at the same levels as the neonate. In summary, this study shows that a selection of post-mitotic tissues down-regulate key apoptotic proteins, in contrast to the thymus, which requires apoptosis for normal function in early adulthood.