During wild-type hermaphrodite development, 131 somatic cells undergo programmed cell death. While many genes involved in the execution of cell death have been identified, the mechanisms that control the commitment of specific cells to undergo apoptosis are poorly understood. To date, mutations in three genes,
ces-1, -2, and -3 (cell death specification), have been found to affect specifically the deaths of particular cells (1).
ces-1 and
ces-2 have been cloned and shown to encode transcription factors (2,3). We intend to perform a genetic screen to seek new ces genes involved in the deaths of the sisters of the PVD neurons in the postdeirid lineage. We have chosen this lineage because the deaths occur during larval development, making them easier to follow by Nomarski optics, and because reporters exist that are likely to be expressed in these cells if their deaths are prevented. Also, the cells of the deirid, although different in lineage, appear similar to those of the postdeirid in morphology, marker expression, and the effects of lineage mutations, thus providing a total of four cells that can be examined for survival in each hermaphrodite. In
ced-3 animals, roughly half of the "undead" PVD sisters contain dopamine, like their "aunt" the PDE cell, as seen by formaldehyde-induced fluorescence (4). We are therefore examining the suitability of a panel of GFP reporters expressed in dopaminergic neurons for use in a screen to identify mutants in which the PVD sisters survive. We also plan to examine whether reporters expressed in the (non-dopaminergic) PVD cell are expressed in its sister cell in a
ced-3 background. We hope that by using GFP reporters we will be able to screen a large number of genomes efficiently, using fluorescence optics and a dissecting microscope, for mutants in which the PVD sisters survive. (1) Ellis, R. E. and Horvitz, H. R. (1991). Development 112: 591-603. (2) Metzstein, M. M., Hengartner, M.O., Tsung, N., and Horvitz, H. R. (1996). Nature 382: 545-547. (3) Metzstein, M. M., Tsung, N., and Horvitz, H. R. (1997). 1997 International Worm Meeting p. 407. (4) Ellis, H. M. and Horvitz, H. R. (1986). Cell 44: 817-829.