2004 West Coast Worm Meeting abstract 181
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| 1 | Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, B.C., Canada |
| 2 | Department of Molecular Genetics, Ohio State University, Columbus, Ohio, USA |
The Notch signaling pathway mediates cell-cell interactions which act to specify cell fate during development. The pathway is well conserved between C. elegans, Drosophila, and humans and many of the components have been well studied. In C. elegans, the LIN-12/Notch receptor is activated by ligands from the Delta/Serrate/LAG-2 family to mediate inductive or lateral cell specification, often via the transcription factor Suppressor of Hairless (Su(H)/LAG-1). Inductive interactions include specification of the Ab.p cell in early embryogenesis and to promote germ line development. Lateral specification occurs during vulval development, specifiying one cell to become the anchor cell (AC) and another to become a ventral uterine precursor cell (VU). lin-12 activity is later involved in the specification of the vulval precursor cells in cooperation with the let-23 receptor tyrosine kinase.
There are many nuclear proteins that have been shown to affect Notch signaling in Drosophila. One of these, strawberry notch (sno), is required specifically for Notch-inductive events including specification of cells in the wing margin, embryonic midline, and the cone cells. The specification of the cone cells requires an inductive signal (Delta) from the neighboring R cells. Activity of sno and the EGF receptor pathway protein ebi are both required to promote Delta expression. Genetic interaction has been demonstrated between ebi and sno, and both appear to act upstream of Notch but downstream of EGF receptor activity. The C. elegans homolog of sno is F20H11.2, Notch signaling pathway homolog 1 (nsh-1). This aspect of Notch signaling has yet to be investigated in C. elegans.
Two alleles of F20H11.2 were isolated in a screen for mutants affecting polarity of the B cell division in males. Normally the B cell divides asymmetrically to produce a large anterior daughter cell and a smaller posterior daughter cell. These daughter cells then differentiate and form neural and structural tissues within the copulatory spicules. nsh-1 animals arrest at the L2 stage. In addition, males exhibit a lack of polarity in the B cell division, as the B cell divides to produce two equal sized daughter cells.
Sequencing has identified a point mutation in the F20H11.2 region for each mutant allele. Further characterization of the mutant phenotype is ongoing and the effect of nsh-1 on other cell lineages investigated. Epistasis experiments using existing mutant alleles and RNAi will help to determine how nsh-1 interacts with known signaling pathways to specify the B cell lineage and other targets.