Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1alpha-deficient mice.

The aim of this study was to clarify the mechanism of apoptosis seen in the cortex of neural cell-specific hypoxia inducible factor-1alpha (HIF-1alpha)-deficient embryos. A previous study showed that the neural cells in the cortical area of the mutant embryos underwent apoptosis coincident with vascular regression. Through histological, immunohistochemical, and electron microscopic technique, two kinds of apoptotic cells were detected in the mutant embryonal cortex. Apoptotic cells of one type were clustered in small round structures, 10-20 mum in diameter, whereas the others, present in large numbers, were distributed in a group at the cortical plate located more to the outer side than the round structures. The histochemical and electron microscopic findings indicate that the former represented the appearance of macrophages, in which cellular fragments including vascular cells underwent oxidative stress-related, TNF receptor-mediated, caspase-2-induced apoptosis, while the latter showed c-Myc-related, caspase-3-activated apoptosis of the neural cells. These results suggest that two pathways of apoptosis are induced in neuronal and vascular cells of the cortex in the neural cell-specific HIF-1alpha-deficient mouse.