CELL-DEATH IN THE EMBRYONIC DEVELOPING LIMB

In amniote vertebrates, the development of form and structure of the l imb bud is accompanied by precise patterns of massive mesodermal cell death with morphological features of apoptosis. These areas of cell de ath appear to eliminate undifferentiated cells which are required only for a limited time period of limb development. Predictable skeletal a nd morphological anomalies of the limb occur when the pattern of cell death is modified in mutant species or under experimental conditions. Most evidence points to the occurrence of local triggering mechanisms to account for the establishment of the areas of cell death and the su bsequent activation of cell death genes. Modifications of the extracel lular matrix and diminution in the contribution of growth factors by n eighbouring tissues appear as the most likely potential candidates for triggering the cell death program. Information on the genetical basis of cell death in the developing limb is very scarce. Among the increa sing number of cell death genes identified in other cell death systems , such as p-53 and the ced-3/ICE and ced-9/bcl-2 gene families, only b cl-2 has been studied in detail during limb development and yet, the i nformation obtained is contradictory. Bcl-2 is not expressed in the ar eas of cell death of the developing limb, but normal limbs develop in mice with disruption of the bcl-2 gene. Obviously, the clarification o f the role of the cell death genes constitute a major task in future s tudies of cell death in the developing limb.