Worm Breeder's Gazette 9(2): 61
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
One fate shared by many cells during C. elegans development is programmed cell death. To examine the mechanisms responsible for determining cell fates, we are studying mutants in which certain cells that normally die instead survive and mutants in which cells that normally survive instead die. For example, mutations in the gene egl- 1 cause the HSNs to undergo programmed cell death. The mutation n703 results in the opposite type of transformation -- it prevents some cell deaths without affecting others. n703 was identified by Nancy Tsung and Carol Trent. Whereas wildtype animals have only two serotonergic cells in the pharynx, the NSMs, they found that n703 worms usually have four. Hilary Ellis examined the pharynx of n703 animals using Nomarski microscopy and saw one, and frequently two, extra nuclei in both the left and right subventral portions of the front bulb. All of the extra nuclei appeared neuronal. These cells could be generated either by extra cell divisions or by the survival of cells that normally die. Although 10 cells die during the development of the neurons of the front bulb of the pharynx, we usually saw the remains of only two dead cells in this region in late ced-2(e1752) embryos. (Mutations in ced-2 cause dead cell bodies to persist). n703; ced-2(e1752) worms lacked even this pair, though most other cell deaths in the head were unaffected. This result indicates that the extra cells in n703 animals may be ones that normally die. Studies of ced-3 worms have suggested that when some cells fail to undergo cell death, they adopt the fates of close relatives . We therefore wondered if the extra cells in n703 animals were closely related to known nerve cells. In the ventral portion of the front bulb of the pharynx there are five classes of nerve cells; three of these, the NSMs, I1s, and I2s, have closely related deaths that if prevented might give rise to extra pairs of cells like those we had observed. Since one pair of extra cells is serotonergic, we expected that these cells might be the surviving sisters of the NSMs (which are also serotonergic). Direct observation confirmed that in n703 animals the NSM sisters do not die at the normal time, and spot checks showed that they survive throughout embryogenesis. The I2 sisters also survive, so we suspect that they may be the other pair of extra cells found in n703 worms. However, additional cell death survivors may also exist. Carol Trent showed earlier that in n703 animals the presence of extra serotonergic cells is a dominant phenotype. We have quantified this dominance by counting nuclei in the pharynx. n703 is 100% penetrant in homozygotes (124/124 animals) and about 94% penetrant in heterozygotes (140/149 animals). Expressivity is variable in both cases, with all four extra cells present much more frequently in homozygotes. We have mapped n703 slightly left of unc-29 on chromosome I (2/13 Unc-29 nonDpy-14 and 3/4 Dpy-14 non-Unc-29 recombinants segregated n703) and are now working to define the null phenotype of the gene.