One of the central questions of developmental biology is how cells generated by cleavage become committed to different developmental fates. This process, termed determination, is poorly understood despite nearly a century of research. One possible mechanism of determination is that maternally specified cytoplasmic components (determinants) are asymmetrically partioned during cleavage and direct specific developmental programs in the cells that receive them. The long term goal of the proposed research is understanding of the cellular and molecular mechanisms of determination. Understanding the basis for the initiation of developmental programs will help to understand how developmental programming can go awry leading to birth defects and cancer. Specifically, the proposed research includes 1) Analysis of the products of five par genes encoding functions required for proper cytoplasmic partitioning in early embryos of the nematode Caenorhabditis elegans, 2) Identification and analysis of genes that interact with the par genes 3) Analysis of three genes involved in determination of the intestine. Analyses will include completion of genetic and phentoypic studies of the five par genes, isolation of DNA corresponding to the genes, computer assisted analysis of the structure of the products of the genes, and analysis of the temporal and spatial distribution of the gene products in situ using antibodies directed against fusion proteins made in E. coli. Genes that interact with the par genes will by identified by mutations that suppress or enhance par mutations. In addition, we will study a new set of genes defined by mutations that appear to specifically block the differentiation, maintenance or determination of intestinal cells. These mutations affect the behavior of the cells in the E lineage, which gives rise exclusively to the intestine, and so are called eli mutations. These two groups of mutations provide a unique opportunity to investigate two aspects of determination in early embryos. The par mutations should provide insight into the mechanism of cytoplasmic localization and the eli mutations should provide information about the mechanism of determination of the intestine.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD027689-02
Application #
3329398
Study Section
Special Emphasis Panel (SRC (08))
Project Start
1991-02-05
Project End
1996-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Watts, Jason S; Morton, Diane G; Kemphues, Kenneth J et al. (2018) The biotin-ligating protein BPL-1 is critical for lipid biosynthesis and polarization of the Caenorhabditis elegans embryo. J Biol Chem 293:610-622
Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth (2013) PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo. Development 140:2005-14
Morton, Diane G; Hoose, Wendy A; Kemphues, Kenneth J (2012) A genome-wide RNAi screen for enhancers of par mutants reveals new contributors to early embryonic polarity in Caenorhabditis elegans. Genetics 192:929-42
Li, Bingsi; Kim, Heon; Beers, Melissa et al. (2010) Different domains of C. elegans PAR-3 are required at different times in development. Dev Biol 344:745-57
Li, Jin; Kim, Heon; Aceto, Donato G et al. (2010) Binding to PKC-3, but not to PAR-3 or to a conventional PDZ domain ligand, is required for PAR-6 function in C. elegans. Dev Biol 340:88-98
Beatty, Alexander; Morton, Diane; Kemphues, Kenneth (2010) The C. elegans homolog of Drosophila Lethal giant larvae functions redundantly with PAR-2 to maintain polarity in the early embryo. Development 137:3995-4004
Aceto, Donato; Beers, Melissa; Kemphues, Kenneth J (2006) Interaction of PAR-6 with CDC-42 is required for maintenance but not establishment of PAR asymmetry in C. elegans. Dev Biol 299:386-97
Beers, Melissa; Kemphues, Kenneth (2006) Depletion of the co-chaperone CDC-37 reveals two modes of PAR-6 cortical association in C. elegans embryos. Development 133:3745-54
Schetter, Aaron; Askjaer, Peter; Piano, Fabio et al. (2006) Nucleoporins NPP-1, NPP-3, NPP-4, NPP-11 and NPP-13 are required for proper spindle orientation in C. elegans. Dev Biol 289:360-71
Aono, Shinya; Legouis, Renaud; Hoose, Wendy A et al. (2004) PAR-3 is required for epithelial cell polarity in the distal spermatheca of C. elegans. Development 131:2865-74

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