Protease activity in programmmed cell death during chick limb development *
Programmed cell death (PCD) is an important process for eliminating unnecessary cells during embryonic development for proper morphogenesis at genetically determined stages. During embryonic limb development, mesenchymal cells in the interdigital regions, as well as in posterior or anterior necrotic zones, are known to die. In this study, we examined the effects of protease inhibitors on PCD in the interdigital regions of chick limb buds to clarify the roles of proteases. Our data using the organ culture system and biochemical assays showed that inhibitors for cathepsin, especially cathepsin L, suppressed the emergence of Nile blue-positive granules, while specific inhibitors for each caspase did not. Extensive studies using the TUNEL assay, conventional histological staining and nucleosomal ladder analysis revealed that inhibitors for cathepsin L did not suppress cell death of the interdigital tissue, but did attenuat phagocytosis of dead cells by macrophages. (Accepted on May 8 , 2003)
