The Antennapedia and Bithorax complexes in Drosophila consist of homeobox containing genes that specify segmental identity. The order of these homeotic genes along the chromosome correlates with the order of expression along the anterior-posterior axis of the embryo. Vertebrate homologues to these genes have been described: they are also arranged in clusters and, as shown in the mouse, the chromosomal organization also correlates with their domains of expression. We are interested in determining whether C. elegans contains a similar complex of homeotic selector genes. Previous work in our lab on
mab-5, an Antp-like homeobox gene responsible for pattern formation in one posterior body region, and more recent work by several labs on
egl-5 and
lin-39 suggest that such a complex may exist. Andrew Chisholm has been analyzing
egl-5, a gene required for-normal fates of several cells in the tail region (WBG 10:2). He has shown that
egl-5 maps 0.03 m.u. to the right of
mab-5 and that the cosmid C08C3 rescues
egl-5 mutants. C08C3 contains both
mab-5 and the homeobox gene
ceh-11, described by Schaller, et al. (Nuc. Acids Res. 18:2033). We have noticed that
ceh-11 has some homology to Drosophila AbdB, consistent with the chromosomal organization in vertebrate clusters and in Drosophila. We are continuing Andrew's rescue experiments, and have now narrowed down the rescuing activity to a 13 kb fragment containing
ceh-11.Sasha Kamb in our lab previously identified a new homeobox gene (
ceh-15) in a PCR screen for more Antp- like homeoboxes. Alan Coulson has recently found that
ceh-15 is positioned to the left of
mab-5 across a gap in the contig map. This is the map position of
lin-39, a good candidate for a gene that functions in the central body region, which Scott Clark has characterized. In
lin-39 hermaphrodites P(3-8) cells do not form a vulval equivalence group and VC neurons but instead behave like P cells in other body regions (S. Clark and B. Horvitz, WBG 11:2). Based on the map position of
lin-39 that Scott provided us, both we and Scott have rescued
lin-39 mutants using cosmids containing Sasha's homeobox,
ceh-15. For our rescue experiments, we injected
lin-39(
mu26) , a new allele isolated recently by Judith Austin in the lab in a screen for Q migration mutants. We have now narrowed down the rescuing activity to a 10 kb fragment that contains
ceh-15. The ceh- 15 homeobox exhibits homology to Drosophila Dfd, again consistent with the organization in flies. We are currently continuing rescue experiments with
ceh-11 and
ceh-15 to determine whether these genes do in fact correspond to
egl-5 and
lin-39 respectively. If there is a '
mab-5 complex' evolutionarily related to the Drosophila clusters, other homeobox genes might be located in the region. In fact, another homeobox gene which has lab-like homology,
ceh-13, is located near
ceh-15. (Schaller, et al., op cit.)) We are now probing about 20 overlapping cosmids spanning the
mab-5 region (
mec-14 to
egl-45) with degenerate homeobox-specific oligos described by Burglin, et al. (Nature 341: 239). Preliminary data suggest that there are several additional Antp-like homeobox genes in this region.