Specification of pharyngeal cell fate depends on
pha-4, which codes for a FoxA transcription factor homologue1,2,3. FoxA proteins have been implicated in gut development in all animals examined, including vertebrates. Despite their importance, few co-factors or upstream regulatory components are known for FoxA proteins in any organism. To identify genes that encode regulators or co-factors of PHA-4, we have undertaken a screen for mutants that suppress a partial loss of
pha-4 function. 27 suppressors from 15,000 haploid genomes were obtained using EMS as a mutagen and 29 more suppressors were found using the Mos1 transposon4. Surprisingly, none of our transposon-induced alleles carried a Mos1 insertion. Secondary tests showed that 16/27 EMS- and 26/29 Mos1-induced alleles were informational suppressors in the smg pathway, leaving 14 non-smg suppressors that likely regulate the activity or expression of
pha-4. The
pha-4 suppressors fall into two classes. All but one of the suppressors are recessive and exhibit a maternal-absence effect. Based on the frequency of isolation, the recessive suppressors are most likely loss-of-function mutations that encode negative regulators of
pha-4 activity or expression. One of the recessive suppressors,
px34, is capable of suppressing
pha-4 lethality as a heterozygote, but homozygotes arrest during larval development, suggesting
px34 defines an essential locus. We have mapped
px34 to linkage group V. The dominant suppressor of
pha-4 lethality,
px63, may be a gain-of-function mutation in a positive regulator of
pha-4 activity or expression.
px63 maps to a different location on linkage group V. We are continuing to map and analyze the
pha-4 suppressors. 1.Mango et al., Development, 120:3019-3031 (1994); 2.Kalb et al., Development, 125:2171-2180 (1998); 3.Horner et al., Genes Dev., 12:1947-1952 (1998); 4.Bessereau et al., Nature, 413:70-74 (2001).