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.

The Mutation n703 Prevents Specific Cell Deaths

R.E. Ellis, J. Sulston, and B. Horvitz

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.