Our lab studies organ development and function. We are interested in understanding the normal processes as well as how improper development and function can lead to problems such as birth defects and cancer. The research in this project looks at the role
ceh-6 plays in the development and function of the excretory system, specifically in the excretory cell. The excretory system is a good organ model system because of its simplicity. The excretory system is composed of four cell types, yet it performs the same functions of osmoregulation and waste removal that mammalian kidneys do. The simple structure enables us to study the development and function at the cellular level. The POU-III homeobox gene
ceh-6 encodes a transcription factor expressed in the excretory cell of Caenorhabdites elegans. Previously, it was shown that
ceh-6 mutants have abnormal excretory cell development and function*. Studies have shown POU-III class homeobox genes are expressed in tissues involved in osmoregulation and secretion of numerous species*. It is believed POU-III proteins regulate proteins involved in osmoregulation and secretion*. Our project studies whether CEH-6 regulates
nac-2, a Na+ coupled transporter found in the excretory cell of Caenorhabdites elegans. First we studied the effects of loss of CEH-6 and ectopic expression of CEH-6 on
nac-2 expression pattern. The study showed
nac-2::GFP expression is lost from all cell types in
ceh-6 deletion mutants. Reciprocally,
nac-2::GFP is ectopically expressed in undifferentiated embryos with ectopically expressed CEH-6. This study indicates CEH-6 either directly or indirectly regulates
nac-2 expression. We are currently analyzing the
nac-2 regulatory sequence to try to identify the region(s) that CEH-6 acts through to regulate
nac-2 expression. We are studying this by deleting large regions of the non-coding sequence and looking for changes in
nac-2::GFP expression. We have found that the excretory cell and rectal epithelial cells expression was markedly reduced and pharynx expression was completely lost when a portion of Intron 1 was removed. We plan to continue the deletion studies to isolate the region of
nac-2 that mediates the response to CEH-6. We also plan to expand this type of study to other transporters expressed in the excretory cell. We hope to define a group of transporters involved in osmoregulation and waste removal regulated by CEH-6.