We have continued our work on the nature and function of nuclear hormone receptors in primitive forms. In the nematode C elegans we have isolated and sequenced the gene chr3 (now known as nhr 23). Transgenic studies with receptor genes show that proper expression requires about 600 base pairs upstream of the first initiation start site and all of the first intron. The transcript initiating upstream of exon I is transpliced to SL1 35 base pairs upstream of the putative methionine initiator. There is a second SL1 splice site bp upstream of the predicted methionine in the second exon. The message from these two splicing reactions appear to be about equal in mixed stage RNA. Antibody studies show that chr3 protein is always localized to the nucleus, is maternally expressed in early development and is almost exclusively expressed in hypodermal cells in embryo and adult. Excess expression of chr3 protein by a heat shock promoter causes loosened cuticle and a blister phenotype. Inhibition of chr3 expression with transgenic RNA produces retained cuticle and disorders of body size regulation. We conclude that chr3 protein is involved in the lysis required for cuticle shedding. It is possible that this may serve as an approach to controlling free living nematodes which are an important pest of potatoes, beets and cotton. We have also continued with studies of cnidaria. Mstr 1 isolated from tripedilia has been sequenced and shown to resemble the RXR family of nuclear receptors; furthermore we have demonstrated that it binds 9cis retinoic acid with nanomolar affinity. Preliminary data suggest that it plays a role in the metamorphosis of planulae into polyps although bioassay of these forms is difficult to control. We also have demonstrated that mstr 1 binds to nucleotide sequences.
| Kostrouchova, Marta; Housa, Daniel; Kostrouch, Zdenek et al. (2002) SKIP is an indispensable factor for Caenorhabditis elegans development. Proc Natl Acad Sci U S A 99:9254-9 |
| Kostrouchova, M; Krause, M; Kostrouch, Z et al. (2001) Nuclear hormone receptor CHR3 is a critical regulator of all four larval molts of the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A 98:7360-5 |
