Comprehensive Analysis of Gene Expression Patterns of Hedgehog-Related Genes

Background: The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity withthe Hedgehog signaling molecule through their C-terminal autoprocessing Hint/Hog domain. Theseproteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteinscontaining only these N-terminal domains. These gene families are called warthog, groundhog, ground-likeand quahog, collectively called hedgehog (hh)-related genes. Previously, the expression pattern of seventeengenes was examined, which showed that they are primarily expressed in the ectoderm.Results: With the completion of the C. elegans genome sequence in November 2002, we reexamined andidentified 61 hh-related ORFs. Further, we identified 49 hh-related ORFs in C. briggsae. ORF analysisrevealed that 30% of the genes still had errors in their predictions and we improved these predictions here.We performed a comprehensive expression analysis using GFP fusions of the putative intergenicregulatory sequence with one or two transgenic lines for most genes. The hh-related genes are expressedin one or a few of the following tissues: hypodermis, seam cells, excretory duct and pore cells, vulvalepithelial cells, rectal epithelial cells, pharyngeal muscle or marginal cells, arcade cells, support cells ofsensory organs, and neuronal cells. Using time-lapse recordings, we discovered that some hh-related genesare expressed in a cyclical fashion in phase with molting during larval development. We also generatedseveral translational GFP fusions, but they did not show any subcellular localization. In addition, we alsostudied the expression patterns of two genes with similarity to Drosophila frizzled, T23D8.1 andF27E11.3A, and the ortholog of the Drosophila gene dally-like, gpn-1, which is a heparan sulfateproteoglycan. The two frizzled homologs are expressed in a few neurons in the head, and gpn-1 isexpressed in the pharynx. Finally, we compare the efficacy of our GFP expression effort with EST, OSTand SAGE data.Conclusion: No bona-fide Hh signaling pathway is present in C. elegans. Given that the hh-related geneproducts have a predicted signal peptide for secretion, it is possible that they constitute components ofthe extracellular matrix (ECM). They might be associated with the cuticle or be present in soluble form inthe body cavity. They might interact with the Patched or the Patched-related proteins in a manner similarto the interaction of Hedgehog with its receptor Patched.