Searching the C. elegans genome project sequence data for genes similar to hedgehog revealed a series of genes which displayed similarity to the carboxy-terminal autoprocessing domain (hog(1) or hint (2)) of hedgehog. Further analysis revealed that several genes had novel domains upstream of the hog domain. Analysis of these novel domains showed that they could occur also without a hog domain. We termed the two new families of genes warthog and groundhog (1). Speculating that the warthog and groundhog genes might act as signaling molecules in a combinatorial fashion during development, we have begun an expression survey of these genes using GFP reporter constructs.
wrt-1 (ZK1290.12),
wrt-4 (ZK678.5) and
wrt-8 (C09F3.d) are expressed in the hypodermal syncytia, as is another gene with a hog/hint domain (2).
wrt-6 (ZK377.1) is expressed in some socket and sheath cells of the anterior sensilla.
wrt-5 (F52E4.6), which has no hog domain, is expressed in various cells including the seam cells, excretory cell and ventral nerve cord motorneurons, the construct has part of the secretory signal sequence left and appears to be trapped in the membrane. For
wrt-2 we have not yet seen expression, though cDNAs do exist. Methionine N-terminal GFP fusions were constructed for
grd-1(R08B4.1) and
grd-7.
grd-1 is expressed in 3 cells adjacent the rectum and
grd-7(F46H5.4) is expressed in motorneurons of the ventral nerve cord. All grd-GFP reporter genes, which were fused at conserved cystein residues of the ground domain (
grd-1,
grd-3,
grd-5 to
grd-9, seem to be secreted into the body cavity so that cell identification is not possible. To summarize, it is clear that the warthog and groundhog genes are not expressed in a combinatorial fashion in a particular cell type (e.g. nervous system). Rather, if these genes play a role in development, they appear to have diverse functions. We will pursue the function of these genes using RNAi and ectopic expression. 1 Burglin TR (1996) Current Biology 6: 1047-1050 2 Wang X et al., 1998 East Coast Meeting Abstract