In C. elegans hermaphrodites, two sex myoblasts (SMs) give rise to the egg-laying muscles. The SMs are born at the end of the first larval stage in the posterior of the animal and migrate anteriorly during the second larval stage to positions that flank the precise center of the gonad. Two mechanisms, one gonad-dependent and the other gonad-independent, are normally involved in guiding the migrations of the SMs. The gonad-dependent mechanism is required for the precise localization of the SMs. In the absence of the gonad, the gonad-independent mechanism is sufficient to guide the SMs to a broad range of positions spanning the center of the animal. Normally both mechanisms cooperate to guide the SMs anteriorly, and only when both mechanisms are compromised do the SMs fail to migrate. We have been able to assess the individual contributions of these two mechanisms by studying SM migration in animals in which one of the two mechanisms has been selectively compromised. Gonad ablation is used to remove the gonad-dependent mechanism, allowing us to study the effects of the gonad-independent mechanism alone. In contrast, mutations in
unc-53 compromise the gonad-independent mechanism and make the migrations of the SMs completely dependent upon the presence of the gonad. In gonad-intact
unc-53 mutants the SMs acquire their normal final positions, but upon gonad ablation the SMs fail to migrate. A temporal analysis of SM migration in wild-type gonad ablated animals and
unc-53 mutants has suggested that the gonad-independent mechanism acts early to move the SMs to positions within closer range of the gonad, while the gonad-dependent mechanism acts later to precisely position the SMs. The fact that the SMs migrate solely in response to the gonad in
unc-53 mutants has allowed us to use this background to screen for mutations affecting the gonad-dependent mechanism. To facilitate this screen, we have taken advantage of the finding that posteriorly displaced SMs give rise to similarly displaced sex muscles. Using an
egl-15::GFP reporter construct that is strongly expressed in a subset of the sex muscles, we have screened for mutants with posteriorly displaced sex muscles in an
unc-53 background. In a screen representing 35,000 mutagenized haploid genomes, we have isolated two general classes of mutations: those which appear to have a primary effect on SM migration, and those which appear to have a secondary effect. The latter class is comprised of 9 mutations conferring a variety of SM cell fate defects. The former class is comprised of 6 alleles of
egl-17, a gene encoding a fibroblast growth factor (FGF), 1 allele of
egl-15, a gene encoding an FGF receptor (FGFR), 1 allele of
pat-3, a gene encoding a b-integrin subunit, and three other weaker mutations which map to distinct genetic loci. We have subsequently demonstrated that EGL-17 (FGF) is capable of attracting the SMs to its site of expression in the center of the animal, supporting our model that EGL-17 is the gonad-dependent attractant. The ability of EGL-17 to precisely position the SMs is dependent upon EGL-15 (FGFR), which has been observed to be expressed in the migrating SMs using GFP reporter constructs. The b-integrin mutant displays both gonad-dependent and gonad-independent migration defects, consistent with the established role of integrins in mediating cell adhesion in migrating cells. We hope to understand how the SM integrates the cues it receives from both the gonad-dependent and gonad-independent mechanisms to result in coordinated cell movement.