Genetic regulation of development and programmed cell death
In living organisms, old cells are constantly dying and being replaced by new cells. Developmental biologists have long-known that cell death is necessary for development, but the ‘suicide process’ by which cells died was uncharacterised until work on the nematode worm, Caenorhabditis elegans, began in the 1970s.
Sydney Brenner established the now widely-used C. elegans, as a model organisim. He realised that fundamental questions about cell division and the development of organs could not be answered by studying complex, higher animals. C. elegans is a small, transparent worm with a short generation cycle. These properties allowed Brenner to study genetic components of the cells and connect them with cell division, cell differentiation and organ development. He was able to induce mutations into specific genes, and follow the resulting changes under a microscope.
John Sulston extended this work, and developed techniques to map every cell division made by C. elegans, from the fertilised egg to all the cells in the simple adult organism. He showed that every nematode underwent exactly the same cell divisions and differentiations. He also found that specific cells always die through programmed cell death, and that this process could be monitored. A breakthrough came when Sulston identified a mutation in a gene that controlled programmed cell death in C. elegans.
Robert Horvitz discovered and characterised particular genes governing programmed cell death in C. elegans. He identified ‘cell death genes’ and showed how different genes interact to bring about the death of the cell. He also found that these genes have equivalents in humans.