LARGE-SCALE NORMAL-CELL DEATH IN THE DEVELOPING RAT-KIDNEY AND ITS REDUCTION BY EPIDERMAL GROWTH-FACTOR

Although normal cell death is known to occur in many developing verteb rate organs, it has not been thought to play an important part in the development of the mammalian kidney. We show here that normal cell dea th is found in both the nephrogenic region and medullary papilla of th e developing rat kidney and, in each of these areas, it follows a dist inct developmental time course. As many as 3% of the cells in these ar eas have a typical apoptotic morphology and the dead cells seem to be cleared rapidly (within 1-2 hours) by phagocytosis by neighbouring par enchymal cells. These values are similar to those in vertebrate neural tissues where 50% or more of the cells die during normal development, suggesting that large-scale death is a normal feature of kidney devel opment. We also show that in vivo treatment with epidermal growth fact or inhibits cell death in the developing kidney, consistent with the p ossibility that the cells normally die because they lack sufficient su rvival factors. Our findings suggest that the extent of normal cell de ath in developing animals is still greatly underestimated and they rai se the possibility that many of these cell deaths may reflect limiting amounts of survival factors.