dc.creator | Von Stetina, Stephen Edward | |
dc.date.accessioned | 2020-08-22T21:16:11Z | |
dc.date.available | 2006-11-07 | |
dc.date.issued | 2005-11-07 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-10262005-161737 | |
dc.identifier.uri | http://hdl.handle.net/1803/14369 | |
dc.description.abstract | Proper function of the brain requires that neurons adopt different morphologies and connections. In the nematode <i>C. elegans</i>, VA and VB motor neurons arise from a common precursor cell but adopt different morphologies and accept input from separate sets of command interneurons. In <i>unc-4</i> mutants, VA motor neurons are miswired with VB-type inputs. We have proposed that miswiring results when VB genes are ectopically expressed in the VAs in <i>unc-4</i> mutants. Previous work revealed that UNC-4 functions with the UNC-37/Groucho co-repressor protein to repress the VB-specific genes <i>acr-5, del-1, glr-4</i>. However, our genetic data rule out roles for these VB genes in synaptic choice. To identify the missing <i>unc-4</i> target genes, a microarray-based strategy for profiling VA motor neurons was adopted.
A comparison of VA-specific transcripts isolated by mRNA-tagging from wildtype and <i>unc-37</i> mutant animals revealed ~250 upregulated transcripts in <i>unc-37</i> animals. One of these genes, <i>ceh-12</i>, is the <i>C. elegans</i> homolog of HB9, a homeodomain transcription factor with conserved roles in motor neuron fate in flies and vertebrates (Arber et al 1999, Broihier and Skeath 2002). In <i>C. elegans, ceh-12</i>::GFP is exclusively expressed in VB motor neurons in wildtype animals. In <i>unc-4</i> and <i>unc-37</i> mutants, <i>ceh-12</i>::GFP is also expressed in VA motor neurons as suggested by the microarray data. Thus, CEH-12 is a strong candidate for an UNC-4 target gene that regulates synaptic choice.
To test this idea, the <i>unc-4</i> promoter was used to drive CEH-12 expression in wildype VA motor neurons. These animals exhibit an Unc-4 like backward movement defect, as expected for a model in which ectopic CEH-12 is sufficient to impose VB type inputs. In addition, we also showed that <i>ceh-12</i> deletion mutants are partial suppressors of Unc-4 movement, thereby confirming that CEH-12 is also required for the Unc-4 miswiring defect. We conclude the VB-specific gene, <i>ceh-12</i>, is normally repressed in VA motor neurons to prevent the imposition of VB-type inputs. The incomplete suppression of <i>unc-4</i>, however, suggests that UNC-4 also controls other downstream target genes that function in parallel pathways to regulate synaptic choice. | |
dc.format.mimetype | application/pdf | |
dc.subject | genomics | |
dc.subject | developmental neurobiology | |
dc.subject | genetics | |
dc.subject | Caenorhabditis elegans -- Nervous system | |
dc.subject | Caenorhabditis elegans -- Genetics | |
dc.title | Genomic strategies reveal a transcriptional cascade that controls synaptic specificity in <i>Caenorhabditis elegans</i> | |
dc.type | dissertation | |
dc.contributor.committeeMember | Richard O'Brien | |
dc.contributor.committeeMember | Randy Blakely | |
dc.contributor.committeeMember | David M. Miller, III | |
dc.contributor.committeeMember | Christopher V. E. Wright | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2006-11-07 | |
local.embargo.lift | 2006-11-07 | |
dc.contributor.committeeChair | David I. Greenstein | |