Two transposon insertion alleles of
ham-2 X,
n1332 and
mu1 (a gift of Cynthia Kenyon), disrupt HSN migration, and a stronger EMS allele found in a non-complementation screen,
ham-2(
gm16), causes larval arrest.
ham-2 encodes a protein, called C07A12.1, with three putative zinc fingers. Sequencing of a cDNA from Yuji Kohara,
yk82h11, confirmed this gene structure. Antibodies to HAM-2 show nuclear staining, and the expression pattern is identical to that seen with
ham-2::GFP constructs. During embryogenesis, HAM-2 is expressed in the HSN and several other neurons in the head and tail. GFP constructs indicate that the first intron of
ham-2 is required for HSN expression. Further, the two transposon insertions, which map to the first intron of the gene, specifically block HAM-2 expression in the HSNs. A screen of HSN migration mutants revealed that mutations in only one gene,
egl-5, prevented expression of HAM-2 in the HSNs.
egl-5;
ham-2 double mutants have no more severe HSN migration defects than
egl-5 mutants alone, consistent with both genes acting in the same pathway. Our data suggest that an enhancer in the first intron of the
ham-2 gene may be required for
egl-5 directed expression of
ham-2 in the HSN, and that the HSN must express HAM-2 for normal cell migration. We are now testing whether EGL-5 can bind sequences from the enhancer region. Although many genes upstream of Hox genes have been found,
ham-2 is the first identified cell migration gene that is a downstream target of a Hox gene. HAM-2 is also expressed in hypodermal cells of embryos in a LIN-26 type pattern, but unlike LIN-26, this expression is transient, disappearing after early elongation. Preliminary results suggest that hypodermal HAM-2 expression is missing in
lin-26(
mc1) mutant embryos.