13细胞衰老与凋亡分析报告.ppt

Brenner provided the basis in a publication from 1974, in which he broke new ground by demonstrating that specific gene mutations could be induced in the genome of C. elegans by the chemical compound EMS (ethyl methane sulphonate). Different mutations could be linked to specific genes and to specific effects on organ development. This combination of genetic analysis and visualization of cell divisions observed under the microscope initiated the discoveries that are awarded by this years Nobel Prize. Mapping the cell lineage John Sulston extended Brenners work with C. elegans and developed techniques to study all cell divisions in the nematode, from the fertilized egg to the 959 cells in the adult organism. In a publication from 1976, Sulston described the cell lineage for a part of the developing nervous system. He showed that the cell lineage is invariant, i.e. every nematode underwent exactly the same program of cell division and differentiation. As a result of these findings Sulston made the seminal discovery that specific cells in the cell lineage always die through programmed cell death and that this could be monitored in the living organism. He described the visible steps in the cellular death process and demonstrated the first mutations of genes participating in programmed cell death, including the nuc-1 gene. Sulston also showed that the protein encoded by the nuc-1 gene is required for degradation of the DNA of the dead cell. Identification of death genes Robert Horvitz continued Brenners and Sulstons work on the genetics and cell lineage of C. elegans. In a series of elegant experiments that started during the 1970s, Horvitz used C. elegans to investigate whether there was a genetic program controlling cell death. In a pioneering publication from 1986, he identified the first two bona fide death genes, ced-3 and ced-4. He showed that functional ced-3 and ced-4 genes were a prerequisite for cell death to be executed. Later, Horvitz showed that another