We want to understand how embryonic cells become committed to particular pathways of differentiation. Molecular and genetic analysis of development in the fruit fly Drosophila and the nematode Caenorhabditis elegans already has resulted in the identification of several key genes involved in determining cell fate. The vertebrate homologs of many of these genes have now been identified, and mutations in some of these homologous genes are associated with tumor formation. Analysis of the function of these genes in model systems like flies and nematodes is likely to provide a better understanding of how the homologous genes function in vertebrates, and possibly suggest therapeutic approaches to correcting functional defects. Although substantial progress has been made in understanding the very early events in the Drosophila embryo, almost nothing is known about the molecules that control early embryogenesis in C. elegans. Because the early development of these two organisms is very different, analysis of embryogenesis in C. elegans should provide a broader understanding of animal development. We have used a genetic approach to identify a small set of genes in C. elegans that appear to play critical roles in determining the fate of early embryonic cells. These genes are named skn-1; skn-2; pie-1; mex-1 and mex-3. The general aim of the proposed work is the molecular analysis of each of these genes and the localization of their gene products in the embryo. skn-1 encodes a protein with a sequence similarity to the DNA-binding domain of a set of transcription factors called BZIP proteins. However in overall structure the skn-1 protein does not resemble BZIP family members and appears to be a novel protein. Experiments are proposed to determine if skn-1 can bind specific DNA sequences, and to identify genes whose products interact with skn-1 to control cell fate. Genetic analysis of pie-1 and skn-2 mutants suggests the products of these genes may interact. Genetic experiments are proposed to identify alleles of pie-1 that will be useful for molecular analysis, as well as other genes that may interact with pie-1. pie-1 and skn-2 mutants lack a particular cell type that mex-3 mutants overproduce. Analysis of mex-3 mutants should provide a better insight into how pie-1 and skn-2 function, and experiments are proposed to complete a phenotypic characterization of the mex-3 embryonic defect.
| Wang, J; Xiao, S H; Manley, J L (1998) Genetic analysis of the SR protein ASF/SF2: interchangeability of RS domains and negative control of splicing. Genes Dev 12:2222-33 |
| Wang, J; Takagaki, Y; Manley, J L (1996) Targeted disruption of an essential vertebrate gene: ASF/SF2 is required for cell viability. Genes Dev 10:2588-99 |
