Cell polarity and cell fate determination in C. elegans.


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2003-2009

FUNDING AMOUNT

1676941 GBP

ABSTRACT

During embryogenesis, patterning events are critical to direct the spatial organisation of the developing animal. I propose to investigate patterning mechanisms that operate in the C. elegans embryo. C. elegans is an excellent system for this work, because powerful genetics and molecular methods can be combined with cell biology to examine developmental controls at single cell resolution. Furthermore, the soon to be completed genomic sequence and rapid reverse genetic methodology are facilitating new avenues of research. I propose to investigate two embryonic patterning events: the early choice of cell division axis orientation, which leads to proper cell positioning and inheritance, and the patterning of posterior tissues later in embryogenesis. The orientation along which a cell divides can be crucial for its subsequent development, and how it is chosen is regulated in organisms ranging from yeast to vertebrates. In C. elegans, where the orientations of early cell division axes are completely reproducible, it is one of the first indications of pattern. In previous work, I showed that the gpb-1 gene, which encodes a beta subunit of heterotrimeric GTP-binding protein, is required for the correct spatial orientation of early embryonic cleavages. In its absence, cell division axes are randomised. This is the only gene known to specifically affect axis orientation, an provides a means for investigating how axes are chosen and what polarity cues are used for orientation. To understand this process better, I propose to study further gpb-1 and identify and characterise molecules with which it interacts. Subsequent patterning events direct the establishment of body plans and the organisation of tissues. I have been studying how the posterior end is patterned. I initially showed that the gene vab-7 encodes an even-skipped homologue required for patterning posterior mesodermal and ectodermal tissues in the embryo. Using this information as a starting point, I have worked out an outline pathway of posterior embryonic patterning. I propose to use genetic and molecular methods to identify and study new genes involved to extend the pathway further, and to investigate the interactions between genes more precisely. This should allow me to understand what patterning means at the molecular and cellular level. vab-7 has a sequence and expression pattern similar to those of even-skipped homologues in other animals, including vertebrates, therefore this work should be directly relevant to other systems. More... »

Related SciGraph Publications

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  • 2009-03. Differential chromatin marking of introns and expressed exons by H3K36me3 in NATURE GENETICS
  • 2008-07. The art and design of genetic screens: RNA interference in NATURE REVIEWS GENETICS
  • 2007-12. Identification of the C. elegansanaphase promoting complex subunit Cdc26 by phenotypic profiling and functional rescue in yeast in BMC DEVELOPMENTAL BIOLOGY
  • 2007-03. RNA interference has second helpings in NATURE BIOTECHNOLOGY
  • 2005-02. Living on the edge in GENOME BIOLOGY
  • 2004-11. Genome-wide RNAi screens in Caenorhabditis elegans: impact on cancer research in ONCOGENE
  • 2004-11. Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans in CELL DEATH & DIFFERENTIATION
  • 2003-12. Involvement of fatty acid pathways and cortical interaction of the pronuclear complex in Caenorhabditis elegansembryonic polarity in BMC DEVELOPMENTAL BIOLOGY
  • 2003-07. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans in NATURE
  • 2003-01. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity in NATURE GENETICS
  • 2003-01. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi in NATURE
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  • 2001-03. Distinct roles for Gα and Gβγ in regulating spindle position and orientation in Caenorhabditis elegans embryos in NATURE CELL BIOLOGY
  • 2000-11. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference in NATURE
  • 2000-01. Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans in GENOME BIOLOGY
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