Coles, Harriet S.R.; (1994) Programmed cell death in the developing kidney and the ubiquity of the programme. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

It has recently been suggested (Raff 1992) that all cells except blastomeres die by programmed cell death unless signalled to survive. In this thesis I explore implications of this idea by asking whether there are cases of developmental cell death that have been overlooked, and whether cell death is induced in many cell types by blocking protein kinase activity and protein synthesis. Normal cell death was not considered to be important in mammalian kidney development. I have found, however, that cell death occurs with distinct time courses, in the nephrogenic region and medullary papilla of the developing rat kidney. Up to 3% of cells in these areas are apoptotic, and are cleared within 1-2 hours by phagocytosis. 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 development. In vivo treatment with epidermal growth factor or insulin-like growth factor inhibits kidney cell death suggesting that this normal cell death may reflect insufficient survival factors. Raff (1992) suggested that all cells depend on survival factors in order to avoid cell death. Blocking protein kinase activity (and consequently cell signalling) and protein synthesis in a variety of neonatal rat tissue explants and preimplantation blastocysts induces 90% cell death within 18 hours. In contrast, blocking protein kinases and protein synthesis in 2-4 cell stage blastomeres does not induce apoptosis. These findings suggest that most cells, except blastomeres, constitutively express the protein components of the cell death programme. I conclude that cell death during vertebrate development is more extensive than was previously thought, that normal cell death may often reflect limiting supplies of survival factors, and that blastomeres differ from even their earliest derivatives in the way cell survival and death are controlled. These findings support the idea that all cells except blastomeres require constant signalling from other cells in order to avoid programmed cell death.

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