Abstract
Apoptosis is a fundamental process in embryogenesis, immune system and tissue homeostasis. Its disregulation may have important implications for congenital anomalies, immune system disorders or tumorigenesis. So, elucidating the molecular mechanism of apoptosis may be important not only in basic science but also for treatment of a range of human diseases. I will briefly review the studies of developmental cell death with special emphasis in cell biological analysis of apoptosis in limb morphogenesis. At first, we have revealed that treatment of embryos with BrdU, a differentiation inhibitor, specifically modified the developmental fate of cells destined to die. Cells in inter-digital necrotic zone (INZ) were rescued from death. Cell cycle and cell death were closely related events and there existed a critical S-phase, which corresponded to the most sensitive time for inhibition of cell death by BrdU. Biochemical examination of DNA of INZ cells revealed the existence of DNA ladders, indicating that dying cells in limb undergo classical apoptosis. The use of microfluorometry coupled with TUNEL method enabled us to detect DNA breaks in individual nuclei very early in the death process. Finally, I will mention the molecules involved in death triggering during morphogenesis.
