Worm Breeder's Gazette 13(4): 40 (October 1, 1994)

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.

Genetic Analysis of sel-10.

E. Jane Albert Hubbard, Iva Greenwald

Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, Columbia University, New York, New York, 10032

  sel-10 is one of a group of genes identified by mutations that suppress and/or
enhance lin-12 mutant phenotypes, and therefore may contribute to cell fate decisions
mediated by lin-12 . sel-10 differs from the other sel genes in several respects. First,
sel-10 alleles are unique in their ability to suppress many defects caused by lin-12 null
mutations: lin-12 (0); sel-10 double mutants are egg-laying defective, but other defects
associated with the reduction or elimination of lin-12 activity (2-anchor cells,
protruding vulva, proximal mitosis, and sterility) are suppressed. Second, unlike
most of the other sel genes, sel-10 does not appreciably suppress the maternal effect
lethality of glp-1 ( e2142 ).Third, mutations in sel-10 are more dramatic enhancers of
lin-12 (d)alleles than are mutations in the other sel genes. For example, lin-12 ( n379
)hermaphrodites are not Multivulva (Muv), but lin-12 ( n379 ); sel-10 ( ar41 )double
mutants show a highly penetrant Muv phenotype. In addition, the lin-12 ( n379 );
sel-10 ( ar41 )combination leads to maternal effect lethality and/or sterility (1). sel-10
mutations also enhance lin-12 ( n379 )phenotypes in the male. While lin-12 ( n379
)males are essentially normal, lin-12 ( n379 ); sel-10 ( ar41 )males display phenotypes
seen in stronger lin-12 (d)alleles: the males are Muv and have ectopic hooks.
  Previous dosage studies of sel-10 ( ar41 )were complicated by the presence of
another loosely linked mutation that made interpretation of the results difficult (1,2).
Therefore we sought to examine the nature of sel-10 mutations in the absence of the
other mutation. Because sel-10 mutants have no obvious phenotype, we have employed
the enhancement of lin-12 ( n379 )to assess the nature of sel-10 ( ar41 )and to map
further the locus. We found that there is an increasing penetrance and expressivity of
the Muv and maternal effect lethal/sterility phenotypes in the following series: lin-12 (
n379 );+< lin-12 ( n379 ); sel-10 /+< lin-12 ( n379 );+/ nDf42 < lin-12 ( n379 ); sel-10 <
lin-12 ( n379 ); sel-10 / nDf42 .The last strain in the series is 100% Muv and maternal
effect lethal and/or sterile. In addition, lin-12 ( n379 )/+; sel-10 / nDf42 is more Muv
than lin-12 ( n379 )/+; sel-10 .From these data we infer that 1) sel-10 is probably
haploinsufficient, since nDf42 /+and sel-10 /+enhance lin-12 ( n379 )somewhat and 2)
that sel-10 ( ar41 )reduces sel-10 activity but does not eliminate it, since sel-10 ( ar41 )/
nDf42 enhances lin-12 ( n379 )more than sel-10 ( ar41 )/ sel-10 ( ar41 ),and nDf42
/+enhances lin-12 ( r379 )more than sel-10 ( ar41 )/+.
  Given that sel-10 ( ar41 )is a loss-of-function mutation, cloning should be
relatively straightforward, as the addition of sel-10 (+)should visibly eliminate the
enhancement of lin-12 ( n379 ).We have mapped sel-10 to the left of him-5 ,between the
cloned polymorphisms arP3 and TCPAR1 .We-are currently injecting pools of cosmids
in an attempt to clone sel-10 and continuing genetic analysis to determine the
functional relationship between sel-10 and lin-12 .
 (1) Sundaram, M. and Greenwald, I., 1993. Genetics 135:765-783
 (2) Sundaram, M. 1993. PhD Thesis, Princeton University