Disease relevance of fem-3

• Mutations in fem-3 resemble alleles of fem-1 (previously characterized): putative null alleles result in complete feminization of XX and XO animals, transforming them into fertile females [1].

High impact information on fem-3

• In adult hermaphrodites (which are producing oocytes), most fem-3 RNA is found in the germ line, consistent with both the requirement for fem-3 in hermaphrodite spermatogenesis and the maternal effects of fem-3 on embryonic sex determination [2].
• Whereas loss-of-function mutants in fem-3 produce only oocytes, hermaphrodites carrying any of nine fem-3 gain-of-function (gf) mutations make none; instead sperm are produced continuously and in vast excess over wild-type amounts [2].
• Expression of fem-3 in the hermaphrodite germ line directs spermatogenesis and must be negatively regulated to allow the switch to oogenesis [2].
• There is no increase in the steady-state level of fem-3(gf) RNA over wild-type, but there is an increase in the polyadenylation of fem-3(gf) RNA that is coincident with the unregulated fem-3 activity [2].
• Male sexual development in the nematode Caenorhabditis elegans requires the genes fem-1, fem-2, and fem-3 [3].

Biological context of fem-3

• We employed RNA interference to show that in all three species, the male-promoting function of fem-3 and its epistatic relationship with its female-promoting upstream repressor, tra-2, are conserved [4].
• Both maternal and zygotic fem-3 activities are required for spermatogenesis in the XX hermaphrodite germline and for male development in somatic and germline tissues XO (male) animals [5].
• Here we show that fem-3 RNA is contributed to embryos as a maternal product and that this RNA is degraded early in embryonic development [5].
• The sequence of fem-3 predicts an open reading frame that could encode a soluble protein; putative fem-3 null mutants truncate this open reading frame [5].
• Second, gld-1 mRNA is initially repressed by FBF (for fem-3 binding factor) to maintain stem cells but then becomes activated by the GLD-2 poly(A) polymerase once stem cells begin to make the transition into the meiotic cell cycle [6].

Anatomical context of fem-3

• The finding of gain-of-function alleles which confer a phenotype opposite to that of loss-of-function alleles supports the idea that fem-3 plays a critical role in germ-line sex determination [7].
• The decision to differentiate as a sperm or an oocyte is regulated by the sex-determining gene, fem-3 [2].

Regulatory relationships of fem-3

• A loss of mog-1 might inappropriately activate fem-3 and thereby abolish the sperm/oocyte switch; its loss might also lead to misregulation of maternal RNAs and thus embryonic death [8].

Other interactions of fem-3

• In Caenorhabditis elegans, fem-1, fem-2, and fem-3 play pivotal roles in sex determination [9].
• While the masculinization is blocked by mutations in sex determining genes required for male development (her-1 and fem-3), the lethality, dumpiness and overexpression of X-linked genes are not, indicating that the effect of sdc-2 mutations on sex determination and dosage compensation are ultimately implemented by two independent pathways [10].
• Previous work showed that at least six mog genes are required for repression by the fem-3 3' untranslated region, and that one of those genes, mog-1, encodes a DEAH-box protein [11].
• The switch from spermatogenesis to oogenesis in the Caenorhabditis elegans hermaphrodite requires mog-6, which post-transcriptionally represses the fem-3 RNA [12].

Analytical, diagnostic and therapeutic context of fem-3

• Results of a titration experiment support the hypothesis that a regulatory factor may bind the fem-3 3' UTR [2].
• Molecular cloning and transcript analysis of fem-3, a sex-determination gene in Caenorhabditis elegans [13].
• However, additional data, including Southern blot analyses on 48 of the strains, indicated that most of the UV radiation-induced fem-3 mutations were not deficiencies, as originally inferred from their homozygous inviability [14].

References