PROGRAMMED CELL-DEATH IN DEVELOPING GRAFTS OF FETAL SUBSTANTIA-NIGRA

Intracerebral transplants of ventral mesencephalic (VM) tissue have be en well characterized. VM grafts contain numerous tyrosine hydroxylase immunoreactive neurons which send axons into the host brain. Transpla nted neurons in VRI grafts develop normally in that they contain tyros ine hydroxylase and GAP43. An overlooked aspect of graft development i s cell death. It has been suggested that cell death in VM grafts was m ostly necrotic. However, recent work in this laboratory suggested that developing grafts contain numerous apoptotic cells. In the present pa per morphological, histochemical, and molecular correlates of apoptosi s were used to assay cell death during VM graft development. At early times (5-15 days) after grafting VM grafts contained numerous apoptoti c cells. In older grafts (21 and 28 days) few apoptotic cells were obs erved, In situ end labeling of fragmented DNA with biotinylated dUTP s howed that early grafts contained numerous positive cells. The express ion of RP8, a molecular correlate of apoptotic cell death, occurred in early grafts, but was not detectable in older grafts. These results i ndicate that apoptosis is a normal part of VM graft development. As in naturally developing neural systems, cell death in grafts may functio n to eliminate cells that fail to connect to appropriate targets. (C) 1994 Academic Press, Inc.