Worm Breeder's Gazette 9(2): 68

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.

fog-2 and Spermatogenesis in Hermaphrodites

T. Schedl, P. Okkema, and J. Kimble

In an effort to further our understanding of germ-line sex-
determination, we have isolated more alleles of the fog-2 locus (fog 
for feminization of the germ-line).  As described at the 1985 CSH 
meeting, XX animals homozygous for fog-2 mutations are female, while 
XO animals are wild-type males.  Thus, this single recessive mutation 
converts C.  elegans from an hermaphrodite to an obligate bisexual 
mode of reproduction.  These observations suggest that the fog-2 
product is required for the brief period of spermatogenesis which 
occurs prior to oogenesis in the hermaphrodite.
Seven independent fog-2 alleles have now been isolated by three 
different protocols; (a) three (q70, q71 and q154) were from screens 
of F1 clones that segregated F2 females, (b)  three (q86, q123 and 
q124) were obtained in complementation screens for F1 females, and (c) 
one (q113) was obtained as a recessive suppressor of the fem-3 gain-of-
function allele q20 (also see below).  All alleles are essentially 
identical.  None are temperature sensitive (although all were isolated 
at 25 C).  No maternal effects are observed - either maternal rescue 
by wild-type product (like fem-1, Diniach and Hodgkin (1984), Dev. 
Biol. 106: 223-235) or zygotic feminization due to maternal absence (
like fem-3, Hodgkin, et. al., (1985), CSHSQB 50: 585-593).  No 
feminization has been observed in males of any age.  In XX animals, 
oogenesis begins among the most proximal germ-line cells at a time 
when spermatogenesis would normally occur.  One allele (q124) is 
slightly leaky with about 1 in 250 XX animals being self-fertile in 
one or both ovotestes.  The fog-2 locus maps very near to unc-51 on 
the tip of the right arm of chromosome V.
Epistasis analysis with the fog-2 allele q71 and putative null 
mutations in other sex-determination loci has yielded the following 
results:  For the fog-2;her-1(e1518) double, XX and XO animals are 
female.  For the fog-2;tra-2(e1425) XX animal, the tra-2 phenotype is 
observed in both the germ-line and the soma.  For the fog-2;tra-1 and 
the fog-2;tra-3 doubles, XX animals show the tra-1 and tra-3 
phenotypes respectively in the soma, while the germ-line phenotype is 
complex and will be discussed elsewhere.  Thus far, phenotypic effects 
of fog-2 mutations are observed in the germ-line but not the soma.
Doniach (WBG Vol. 8, #3, p. 34 and Genetics, in press) has 
previously suggested that a gene(s) might negatively modulate the tra-
2 gene or gene product so as to allow the fem genes to be temporarily 
active resulting in the brief period of spermatogenesis in the 
hermaphrodite germ-line.  The fog-2 gene product is an excellent 
candidate for a negative regulator of tra-2 based on both the fog-2 
mutant phenotype and the fact that tra-2 mutations are epistatic to it.

The phenotype of the fog-2;her-1 double mutant suggests that the fog-
2 product is expressed/active regardless of the X/A ratio.  This could 
be a result of fog-2 being normally active in both XX and XO animals.  
The fact that spermatogenesis is uneffected in fog-2 XO mutant could 
then be a consequence of fog-2 function being redundant in males or 
that we do not yet have a null allele.  Alternately, fog-2 could be 
active only in the absence of her-1.Note:  That a her-1 mutant XO is 
an hermaphrodite and that in XX animals, the her-1 gene or product is 
thought to be inactive (Hodgkin, (1980), Genetics, 96: 649-664).
In the course of complementation screens for new fog-2 alleles, two 
other mutations were recovered from F1 females.  The first, q126 is a 
mutation with a fog phenotype that is distinct from fog-2.  Both XX 
and XO animals have feminized germ-lines.  In XX animals, the 
feminization is semidominant, although it is slightly leaky in q126 
homozygotes.  In XO animals, the germ-line has first sperm and the 
oocytes; q126 maps in the region of unc-13 to unc-29 on chromosome I.
The second mutation, q122, is a dominant gain-of-function (gf) tra-2 
allele.  It was shown to be a tra-2 allele by map position and by 
isolation of intragenic revertants that have the tra-2 loss-of-
function masculinizing phenotype which fail to complement canonical 
tra-2 alleles.  The phenotypes of q122 are similar to those of the tra-
2(gf) allele e2020 described by Doniach (op. cit.): (a)  q122 XX 
animals homozygous, heterozygous or in trans to a tra-2 null are 
female.  (b) q122 XO animals are wild-type males, although some begin 
to make oocytes and yolk (as judged by Nomarski) when old.  Like fog-2 
mutants, tra-2(q122gf) male/female strains can be constructed.
Furthermore, both the fog-2 allele q71 and the tra-2(gf) allele q122 
are unselected suppressors of fem-3 gain-of-function mutations.  In XX 
animals, fem-3(gf) alleles completely masculinize the germ-line so 
that spermatogenesis and no oogenesis occurs (Barton, et. al., (1985), 
CSH, p. 97).  In both the fog-2(q71);fem-3(q20gf) and the tra-2(q122gf)
;fem-3(q20gf) double mutants self-fertility is restored  (q71 is a 
recessive suppressor while q122 is a dominant suppressor).
In summary, the similiarities between fog-2 loss-of-function and tra-
2 gain-of-function phenotypes are consistent with the idea that fog-2 
negatively regulates tra-2 which in turn negatively regulates the fem 
genes to allow hermaphrodite spermatogenesis.