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Comments on Dustin L Updike et al. (2003) International Worm Meeting "Suppressors of pha-4/FoxA loss of function mutations define potential pha-4 regulators" (0)
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Dustin L Updike, & Susan E Mango (2003). Suppressors of pha-4/FoxA loss of function mutations define potential pha-4 regulators presented in International Worm Meeting. Unpublished information; cite only with author permission.
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).