Proper function of the brain requires that neurons adopt different morphologies and connections. Specific gene regulation is likely to mediate these events. In the nematode C. elegans, mutations in the UNC-4 homeodomain transcription factor miswire the motor neuron circuit and disrupt movement. UNC-4 and the Groucho-like cofactor UNC-37 function together in the affected motor neurons to repress target genes, a subset of which controls synaptic specificity. The goal of this project is to identify these genes. The promoters of two known UNC-4 targets (acr-5 and del-1), which do not regulate synaptic choice, will be analyzed to define UNC-4 Response Elements (U4RE) that mediate repression. Upstream regions will be deleted to identify sequence motifs that are required for unc-4 regulation. Identified U4REs will be used in gel shift experiments to determine if UNC-4 binds directly to these sites, which should also be present in other unc-4 regulated genes. Since UNC-4 and UNC-37 function as repressors, targets genes should be elevated in unc-4 and unc-37 mutants (compared to wildtype). The full genome C. elegans microarray will be probed to detect these differentially expressed genes. The promoters of candidate targets will be scanned for U4REs. Genetic methods will be used to test authentic UNC-4 targets for their roles in the synaptic specificity pathway that UNC-4 regulates.
| Fox, Rebecca M; Watson, Joseph D; Von Stetina, Stephen E et al. (2007) The embryonic muscle transcriptome of Caenorhabditis elegans. Genome Biol 8:R188 |
| Von Stetina, Stephen E; Watson, Joseph D; Fox, Rebecca M et al. (2007) Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system. Genome Biol 8:R135 |
| Von Stetina, Stephen E; Fox, Rebecca M; Watkins, Kathie L et al. (2007) UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes Dev 21:332-46 |
| Touroutine, Denis; Fox, Rebecca M; Von Stetina, Stephen E et al. (2005) acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. J Biol Chem 280:27013-21 |
| Fox, Rebecca M; Von Stetina, Stephen E; Barlow, Susan J et al. (2005) A gene expression fingerprint of C. elegans embryonic motor neurons. BMC Genomics 6:42 |
