Dissection of Genetic Pathways in C. elegans - Caenorhabditis Elegans: Molecular Genetics and Development - page 146

Fig. 10 Schematic diagramof the genetic pathway leading to gcy-5 expression inASER neuron. Despite
bilaterally morphological symmetry, the ASEL and AESR neurons display distinct chemosensory capac-
ities that correlatewith the left-right asymmetric expression of three putative sensory receptor genes, gcy-5,
expressed only in ASER, and gcy-6 and gcy-7 (not shown here) expressed only in ASEL ( Chang et al.,
2003 ). A cascade consisting of a microRNA and several transcription factors act sequentially to restrict gcy-
5 gene expression to the ASER: a microRNA encoded by lsy-6 gene, the homeobox transcription factors
cog-1, ceh-36,andlim-6, and the transcriptional cofactors unc-37/Groucho and lin-49. In ASEL and ASER,
a tightly balanced antagonistic effect between a repressor (COG-1/UNC-37) and a putative activator (CEH-
36/LIN-49) complex regulates expression of lim-6 ( Chang et al., 2003 ). In ASEL, lsy-6 acts by targeting a
complementary site in the cog-1 3 ' UTR to repress cog-1 expression. CEH-36/LIN-49 then induces
expression of lim-6, which subsequently represses expression of gcy-5. Thus, ASEL normally does not
express gcy-5.InASER,lsy-6 is not expressed. The raised activity of COG-1/UNC-37 represses expression
of lim-6 by overcoming CEH-36/LIN-49-mediated induction of lim-6 expression. Consequently, LIM-6-
mediated repression of gcy-5 expression is released, which leads to the differential expression of gcy-5 in
ASEL and ASER. More details about this pathway can be found elsewhere ( Hobert, 2006 ). (For color
version of this figure, the reader is referred to the web version of this topic.)
F. Functional Genomic Approaches for Gene Ordering
The functional genomic approaches discussed above are not only effective in
identifying genes that regulate a particular biological process, but also useful in
ordering these genes, because some functional genomic approaches by their nature
reveal the hierarchical relationships between components of pathways. For example,
in Section II.B.2., Budovskaya et al.(2008) bioinformatically searched for transcrip-
tion factors that act upstream to control expression of several hundred genes that were
found to share similar age-regulated expression changes identified by their DNA
microarray analysis. In this study, the direction of the searching strategy was from
the age-regulated target genes (downstream) to transcription factors (upstream). Once