The objective of this proposal is to understand the genetic control of cell identity and terminal differentiation. Genes have been identified for the establishment of cell identity, for effecting terminal differentiation, and for the differentiated features of the touch receptor neurons in the nematode Caenorhabditis elegans. One of these genes, mec-3, appears to effect terminal differentiation by inducing transcription of genes encoding the differentiated features of the touch receptors. The proposed experiments examine how mec-3 is regulated, and how mec-3 in turn regulates expression of other genes. Transformation of C. elegans by microinjection of DNA will be used to study the regulatory and coding regions of mec-3, to express mec-3-1acZ fusions in C. elegans to determine the localization of mec-3, to overproduce mec- 3 and express it in other tissues, and to examine genes that are regulated by mec-3. New genes that affect mec-3 will be identified, then characterized and cloned along with existing genes. Anti-mec-3 antibodies will be generated and used to determine localization of mec-3 in wild-type and mutant strains. Understanding cell determination and differentiation, as addressed in this proposal, relates to three aspects of human health: 1) Essentially all cells in the human body undergo these processes. 2) The brain is the most complex human organ, with the largest number of cell types. Some mental deficits and neuronal diseases may be due to defects in determination and differentiation of specific cell types in the brain. 3) Cancer is defined by the failure of cells to stop dividing and differentiate. mec-3 appears to induce terminal differentiation and is associated with (and perhaps causes) a cessation of cell division. Cancers may occur, in part, from a failure to express genes such as mec-3.
