Worm Breeder's Gazette 9(2): 70

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.

Screens for Maternal-Effect Lethal Mutations Affecting the Gut Lineage

D. Morton, S. Sprunger, and K. Kemphues

In an effort to understand the mechanism of determination in early C.
elegans development, we have been using a screen devised by J.  
Priess et al.  (C.  elegans newsletter 8, #2, 5) to identify maternal-
effect lethal (mel) mutations that affect the early embryonic cleavage 
pattern.  This procedure requires first identifying the mel mutants, 
maintaining them in stock by selection, then observing early cleavages 
in embryos from mutant homozygotes of each strain.  This approach has 
resulted in the identification of several mutants with aberrant 
cytoplasmic partitioning, defining three loci, designated par-1,2,3 (
Kemphues and Priess, Abstracts, 1985 C.  elegans meeting, p15).  
However, because of the low frequency of par mutants among the total 
pool of maternal effect lethals, observing early development is not an 
efficient way to obtain large numbers of mutants with this phenotype.  
In addition, there may be mel mutants that affect determination 
without detectably affecting cytoplasmic partitioning.  In an effort 
to overcome these problems we have begun to screen for mels that 
produce embryos arresting with large numbers of cells but which do not 
differentiate gut cells.  This can be done very simply by scoring 
newly identified mel homozygotes (which are bags of dead embryos) 
under polarized light to visualize gut granules.  Gut granules 
normally appear in cells of the gut lineage at about the 200 cell 
stage of embryogenesis.  Mutants that produce embryos with large 
numbers of cells but no visible gut granules are potentially defective 
in some step in the determination or differentiation of the gut.  In 
this screen, those mels that produce embryos with gut granules are 
discarded as are mels producing embryos with no gut granules and 
obviously small numbers of cells.  We expect to find at least three 
interesting classes of mutations in such screens: 1) New alleles of 
par-1.  Mutations in par-1 (b274, e2012) have been shown to affect 
partitioning of cytoplasm in the early cleavages and lead to arrested 
embryos with many differentiated cells, but no detectable gut granules.
2) Mutations in other loci that affect partitioning of cytoplasm.  
Because cytoplasmic localization appears to be important for gut 
determination, multiple loci controlling localization could mutate to 
a similar terminal phenotype.  3) Mutations that specifically affect 
the determination or differentiation of the gut.  If there are 
maternally expressed molecules with a unique function in the 
determination or differentiation of the gut, mutations in genes 
encoding these molecules should surface in our screens.  Our initial 
results are promising.  We have screened roughly 3000 F1 clones from 
mutagenized adults and have identified four mel mutants whose progeny 
arrest in embryogenesis with large cell numbers but no gut granules.  
One of the mutants (it32) is a new allele of par -1 
Two other mutations identify a new locus par-4 (it33, it47) V (near 
dpy-21).  Progeny from par-4 mutants are defective in P granule 
localization and have synchronous early cell divisions, defects common 
to all par mutants.  However, par-4 mutants differ from mutants at the 
other par loci in that the first division results in nearly normal 
size asymmetry.  The fourth mutant has no obvious partitioning defect, 
but early divisions are slowed about two-fold compared to wild-type.  
Relative timing of divisions is normal, and the E lineage is normal at 
least to the 8 E-cell stage.  The low frequency at which these mutants 
arise, coupled with the relative ease of screening should make it 
possible for us to satura   te the genome for loci that can mutate to 
this phenotype.