The HSNs are a pair of serotoninergic motor neurons that innervate the egg-laying muscles and stimulate hermaphrodites to lay eggs. The HSNs are generated in the tail of the embryo and then migrate anteriorly to positions near the middle of the animal. Two genes required for the HSN migrations are ham-l IV and
egl-43 II. As in many of the HSN migration mutants, the HSN migration defect in ham-l animals appears to reflect a more fundamental defect in HSN identity. The development of both the HSN and the sister cell of the HSN, the phasmid neuron PHB, is abnormal in ham-l animals. The ham-l HSN and PHB phenotypes have led us to propose that ham-l is required for the distribution of developmental potential between the sister cells HSN and PHB. Genetic analysis of the ham-l gene suggests that these phenotypes result from the loss or reduction of ham-l activity. We have localized the ham-l gene to a region of 12 kbp using a combination of RFLP mapping and germline transformation. This region encodes a 1.8 kb poly(A)+ RNA that appears to be the ham-l mRNA. Sequencing of a cDNA representing most of the ham-l mRNA shows that this cDNA contains a single long open reading frame that shares no signiflcant sequence similarity to sequences in the gene banks. Mutations in
egl-43 result in the most severe HSN migration defect of all HSN migration mutants but do not strongly affect other aspects of HSN development. These observations suggest that the HSN migration defect in
egl-43 mutants might reflect a defect in HSN migration per se. This possibility is particularly interesting since
egl-43 mutants are norrnal for other cell migrations that occur during worm development. This specificity for HSN migration is not a consequence of residual
egl-43 activity remaining in these mutants. Animals homozygous for several small deficiencies that fail to complement egl- 43 mutations hatch and then arrest as Ll larvae. Other than the HSN migration defect, no other embryonic cell migrations are affected in these homozygous deflciency animals. These results suggest that the
egl-43 gene product is not involved in some general aspect of cell migration. In the process of characterizing deficiency endpoints in the region of
mab-3 II, Caroline Shamu and Michael Shen mapped the right endpoints of mnDf60 (which complements
egl-43) and mnDf28 (which fails to complement
egl-43) to the cosmid R53. Using germline transformation, we localized the
egl-43 gene to a 5.5 kbp subclone contained within R53. Analysis of the transcripts from this region and additional germline transformation experiments suggest that the
egl-43 gene encodes a pair of transcripts. Sequencing of this region shows that these transcripts define a protein product or products that are closely related to a Zinc finger protein encoded by the mouse evi-l locus. This locus is the site of retroviral insertions that lead to leukemia in mice. These results suggests that
egl-43 is playing a regulatory role in HSN migration, perhaps by transcriptionally controlling genes that function directly in HSN migration.