GENETIC ANALYSIS OF MORPHOGENESIS IN A NEMATODE

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The aim of this research is to understand how genes determine the morphology of animals. A genetic and molecular approach to this problem is taken using the nematode Caenorhabditis elegans. C elegans is a model organism amenable to genetic analysis that is also useful for developmental biological research because of its fixed cellular anatomy and cell lineages, and because the sequence of its genome is being determined. Many genes identified in model organisms such as C elegans are known to play roles in human disorders such as cancer and birth defects. Study of morphological mutants of C elegans has shown that HOX genes determine the morphology of a set of serially-repeated neuronal structures known as rays. HOX genes, present in all animals, encode conserved homeodomain trascription factors that pattern the anteroposterior body axis as well as other structures such as limbs. How HOX genes help to determine the morphology of rays will be determined by studying the expression of one HOX gene, egl-5, in wild type and in mutants. Regulated expression of egl-5 is necessary for specification of the morphological identities of the rays. Expression of egl-5 will be assayed by means of reporter genes, antibody staining, and in situ RNA hybridization. New mutant screens will be carried out to identify additional genes that regulate the expression of egl-5. The aim is to understand how egl-5 expression is confined to only certain branches of a cell lineage by identifying the factors that regulate its expression. The molecular properties of two additional genes that act along with egl-5 to specify ray identities will be determined by cloning and sequencing.