In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to Sank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devi Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

The development of a multicellular organism requires the corrrect positioning of many different cell types. Cell migration, which is a common feature of metazoan development, allows cells generated in one position to function elsewhere. While most cells in the nematode Caenorhabditis elegans are generated in their final positions, a number of cells undergo lengthy migrations (Sulston and Horvitz, 1977; Kimble and Hirsh, 1979; Sulston et al. 1983; Hedgecock et al. 1987). We have focused on the migrations of the sex myoblasts (SMs), the progenitors of the 16 vulval and uterine muscle cells of the hermaphrodite (Sulston and Horvitz, 1977), to study how migrating cells are correctly positioned. Two SMs, one in each of the left and right longitudinal ventral muscle quadrants, are generated midway along the posterior portion of the body region of late first larval stage animals. These cells then migrate anteriorly approximately 65 microns (about 20 % of the length of the animal) along the muscle quadrants to positions that laterally flank the precise center of the gonad. After the SMs assume their final positions, they generate the muscle cells required for egg laying.

A role of the gonad in regulating the migrations of the SMs was first revealed by the mutation dig-l(nl321), which results in the anterior, and occasionally dorsal, displacement of the gonad (Thomas et al. 1990). In dig-1 animals, the SMs can adjust both the extent and the direction of their migrations, so that they assume positions that precisely flank the center of the displaced gonad, even if it is located dorsally. Destroying the somatic gonad in both wild-type and dig-1 animals revealed that a signal from the somatic gonad attracts the SMs to flank the precise center of the gonad (Thomas et al. 1990). In the absence of this signal, the SMs still migrate anteriorly to approximately normal positions as a result of a gonad-independent mechanism that controls their migrations (Thomas et al. 1990). Thus, two mechanisms control the migration of the SMs: gonad-independent cue(s) guide the SMs to a broad range of possible final positions near the center of the animal, while a gonad-dependent attractive signal apparently serves to focus tightly the final positioning of the SMs.

Animals with defective SMs are unable to lay eggs (Trent et al. 1983; M. Stem and R. Horvitz, manuscript in preparation). Such animals bloat with unlaid eggs that hatch internally and form ‘bags of worms.’ This phenotype has been used to isolate mutations that affect the development of the sex muscles (Trent et al. 1983; M. Stem and R. Horvitz, manuscript in preparation). Mutations in two genes that perturb the migrations of the SMs cause these cells to stop prematurely, approximately midway along their normal routes. We propose that the SM migration is arrested as a result of a repulsion that emanates from the somatic gonad, which is the normal destination of the SMs and the source of an attractive signal in wild-type animals.

Microscopy and laser ablation

Living animals were observed using Nomarski differential interference contrast microscopy; cell nomenclature and cell lineage analysis follows the method of Sulston and Horvitz (1977). Nuclei were destroyed by a laser microbeam (ablated) as described by Avery and Horvitz (1987). Early first larval stage hermaphrodites were mounted in a 3.5μI drop of M9 salts (Brenner, 1974) on an 5 % agar pad containing 10 mM sodium azide (an anesthetic), and a coverslip was placed on them while they were still thrashing so that they would He in a lateral-up position. Ablations of the somatic gonadal precursor cells, Zl and Z4, were confirmed the following day by scoring the size of the gonad, which contained only a few germline ceUs, and the state of the central vulval precursor cells (P5.p, P6.p and P7.p), which are normally induced to undergo multiple rounds of division only in the presence of the gonadal anchor ceU (Kimble, 1981). Ablations of subsets of the Zl and Z4 ceU descendants (see the legend to Fig. 3 for nomenclature) were confirmed for the successful destruction of the appropriate cells within a few hours after recovery from the anesthetic by Nomarski microscopy. All animals were observed the following day for the positions of their SMs, which were scored relative to the positions of the vulval precursor cells, as described by Thomas et al. (1990). In the cases in which the vulval precursor cells were absent as a result of the ablation of their precursors, the positions of the SMs were scored with respect to the positions of the anchor cell, P9.p, and the nearby body muscle cells.

Statistical analysis

The significance of differences between distributions of the SMs were determined using a one-tail unpaired t-test. In the cases in which there were possible non-normal distributions (Zl, Z4 and Zl.pa/Z4.ap ablations), the non-parametric Mann-Whitney U-test was also applied. The P value given in the text represents the highest P value obtained for both mutants for all tests appfied. For these statistical tests, the position indicated by each hash mark in the figures was converted to a number proportional to the distance between the SM and the center of the gonad.

C. elegans hermaphrodites lacking vulval and uterine muscles are severely egg-laying defective and are resistant to both serotonin and imipramine, drugs that induce egg laying in wild-type animals (Trent et al. 1983). A set of 145 egg-laying defective mutants identifying more than 64 genes had previously been isolated and classified based on their responses to serotonin and imipramine (Trent et al. 1983). Those mutants that either failed to respond (class A) or had a variable response (class E) to these drugs were considered to be candidates to have defective SMs. In fact, two of these mutants, egl-31(n472) (which fails to generate the SMs) and egl-15 (n484) (which has mispositioned SMs) were previously found to have defective SMs (P. Sternberg, as cited in Trent et al. 1983). We therefore examined the remaining class A and class E egg-laying defective mutants by polarized fight (Waterston et al. 1980) to identify other mutants that had missing or misplaced vulval muscles. Only one additional strain, egl-17(el313), lacked vulval muscles in their normal positions. Examination of the SM nuclei in third:stage larvae using Nomarski optics revealed that both egl-15 and egl-17 mutants have posteriorly displaced SMs (Figs 1, 2A). Both the egg-laying defect and the mispositioning of the SMs are recessive phenotypes of egl-15(n484) and egl-17(el313) animals (data not shown), as well as of animals bearing additional alleles of egl-15 and egl-17 that have been isolated and have similar effects upon the positioning of the SMs (M. J. Stem and H. R. Horvitz, manuscript in preparation).

Fig. 1.

Nomarski photomicrographs of the SMs in (A) a wild-type and (B) an egl-15(n484) mid-third larval stage hermaphrodite. Each pair of photographs shows a lateral view of the same anaesthetized animal seen in different planes of focus. The SMs are shown after their first divisions to ensure that they had finished their migrations. No significant movement of the SM descendants occurs until after the SMs have completed their normal three rounds of divisions. Dorsal is at the top, and anterior is to the left. Nuclei connected by bars are the daughters of the designated blast cell. In the wild-type animal, the midpoint between the daughters of the SM lies directly lateral to both the anchor cell nucleus (arrowhead), which is located at the center of the gonad, and the midpoint between the daughters of the central vulval precursor cell P6.p. In the egl-15 animal, the midpoint between the daughters of the SM lies far posterior to the anchor cell, lateral to the midpoint between the daughters of a more posterior vulval precursor cell P8.p (which lie in a different plane of focus). The SM positions in egl-17 mutants are similar to those in egl-15 mutants (see Fig. 2A). Scale bar represents 20μ m.

Fig. 1.

Nomarski photomicrographs of the SMs in (A) a wild-type and (B) an egl-15(n484) mid-third larval stage hermaphrodite. Each pair of photographs shows a lateral view of the same anaesthetized animal seen in different planes of focus. The SMs are shown after their first divisions to ensure that they had finished their migrations. No significant movement of the SM descendants occurs until after the SMs have completed their normal three rounds of divisions. Dorsal is at the top, and anterior is to the left. Nuclei connected by bars are the daughters of the designated blast cell. In the wild-type animal, the midpoint between the daughters of the SM lies directly lateral to both the anchor cell nucleus (arrowhead), which is located at the center of the gonad, and the midpoint between the daughters of the central vulval precursor cell P6.p. In the egl-15 animal, the midpoint between the daughters of the SM lies far posterior to the anchor cell, lateral to the midpoint between the daughters of a more posterior vulval precursor cell P8.p (which lie in a different plane of focus). The SM positions in egl-17 mutants are similar to those in egl-15 mutants (see Fig. 2A). Scale bar represents 20μ m.

Fig. 2.

Positions of the SMs in animals of various genotypes shown relative to the body of the worm. Schematic diagrams of a lateral view of an early third larval stage (A) wild-type and (B) dig-1 hermaphrodite is shown at the top of each panel. The cell body of the SM is shown at the position of its generation late during the first larval stage, and the arrow indicates the direction, route and extent of the SM migration during the second larval stage. Anterior is left, and dorsal is up. Each hash mark represents the final position of a single SM, and the vertical arrow indicates the position of the anchor cell, which lies at the center of the gonad. The metric depicts the approximate positions of the Pn.p cell nuclei, P2.p-P9.p, which are aligned with the diagrams of the worm to indicate their approximate antero-posterior positions. In wild-type animals, the anchor cell is always aligned with P6.p. Iri dig-1 animals, the absolute position of the gonad is shifted anteriorly to various extents, and, hence, the arrow represents the average position of the anchor cell. The SM positions are shown with respect to the center of the gonad in distances of Pn.p cell equivalents. Only data from dig-1 animals with ventral gonads are shown. The final positions of the SMs were determined as described previously (Thomas et al. 1990). The control data for wildtype and dig-1 animals are from Thomas et al. (1990) and are shown for comparison. The alleles used were dig-l(nl321), egl-15(n484), and egl-17 (el313).

Fig. 2.

Positions of the SMs in animals of various genotypes shown relative to the body of the worm. Schematic diagrams of a lateral view of an early third larval stage (A) wild-type and (B) dig-1 hermaphrodite is shown at the top of each panel. The cell body of the SM is shown at the position of its generation late during the first larval stage, and the arrow indicates the direction, route and extent of the SM migration during the second larval stage. Anterior is left, and dorsal is up. Each hash mark represents the final position of a single SM, and the vertical arrow indicates the position of the anchor cell, which lies at the center of the gonad. The metric depicts the approximate positions of the Pn.p cell nuclei, P2.p-P9.p, which are aligned with the diagrams of the worm to indicate their approximate antero-posterior positions. In wild-type animals, the anchor cell is always aligned with P6.p. Iri dig-1 animals, the absolute position of the gonad is shifted anteriorly to various extents, and, hence, the arrow represents the average position of the anchor cell. The SM positions are shown with respect to the center of the gonad in distances of Pn.p cell equivalents. Only data from dig-1 animals with ventral gonads are shown. The final positions of the SMs were determined as described previously (Thomas et al. 1990). The control data for wildtype and dig-1 animals are from Thomas et al. (1990) and are shown for comparison. The alleles used were dig-l(nl321), egl-15(n484), and egl-17 (el313).

Fig. 3.

Effect of gonadal cell ablations on the final positions of the SMs. (A) Somatic gonadal cell lineages that occur prior to the migrations of the SMs (Kimble and Hirsh, 1979), and a schematic dorsal view of the positions of these cells in a late second stage larva (Kimble and Hirsh, 1979), the stage at which the SMs complete their migrations. In the lineage diagrams, anterior daughters are to the left, and posterior daughters to the right, dtc, distal tip cell; ss, precursor of the sheath and spermatheca; DU, precursor of the dorsal uterus; VU, precursor of the ventral uterus; ac, anchor cell. A, anterior; P, posterior; L, left; R, right. The thick outer lines indicate the hypodermal wall of the animal, and the inner structure represents the gonad. The arrows indicate the paths of the normal SM migrations. (B,C,D) The final positions of the SMs in wild-type, egl-15, and egl-17, animals, respectively, represented as described in the legend to Fig. 2. The data in (B) are from Thomas et al. (1990) and are shown for comparison. Cells Ablated, cells destroyed by laser microsurgery: Z1,Z4 and Z2,Z3 are the somatic and germline gonadal blast cells, respectively; P3-P8 are the blast cells P3/4, P5/6 and P7/8 on both sides of the early first stage larva (Sulston and Horvitz, 1977). Cell nomenclature has been described by Sulston and Horvitz (1977); letters to the right of the period represent either the anterior ‘a’ or posterior ‘p’ daughter.

Fig. 3.

Effect of gonadal cell ablations on the final positions of the SMs. (A) Somatic gonadal cell lineages that occur prior to the migrations of the SMs (Kimble and Hirsh, 1979), and a schematic dorsal view of the positions of these cells in a late second stage larva (Kimble and Hirsh, 1979), the stage at which the SMs complete their migrations. In the lineage diagrams, anterior daughters are to the left, and posterior daughters to the right, dtc, distal tip cell; ss, precursor of the sheath and spermatheca; DU, precursor of the dorsal uterus; VU, precursor of the ventral uterus; ac, anchor cell. A, anterior; P, posterior; L, left; R, right. The thick outer lines indicate the hypodermal wall of the animal, and the inner structure represents the gonad. The arrows indicate the paths of the normal SM migrations. (B,C,D) The final positions of the SMs in wild-type, egl-15, and egl-17, animals, respectively, represented as described in the legend to Fig. 2. The data in (B) are from Thomas et al. (1990) and are shown for comparison. Cells Ablated, cells destroyed by laser microsurgery: Z1,Z4 and Z2,Z3 are the somatic and germline gonadal blast cells, respectively; P3-P8 are the blast cells P3/4, P5/6 and P7/8 on both sides of the early first stage larva (Sulston and Horvitz, 1977). Cell nomenclature has been described by Sulston and Horvitz (1977); letters to the right of the period represent either the anterior ‘a’ or posterior ‘p’ daughter.

Despite the mispositioning of the SMs in egl-15 and egl-17 mutants, many aspects of the subsequent development of these cells are normal. The SMs grow and divide as in the wild type, generating the correct number of descendants. The descendant cells appear to differentiate correctly, since, like normal egg-laying muscles, they stain with antibodies (Miller et al. 1983; Ardizzi and Epstein, 1987) directed against muscle myosin (data not shown) and they twitch, as can be observed with Nomarski microscopy. However, the descendant muscle cells neither make their normal attachments nor function in egg laying, presumably because they are too far displaced. Thus, the mispositioning of the SMs could account for the egg-laying defects of egl-15 and egl-17 mutants.

We used Nomarski optics to follow the migrations of the SMs in living egl-15 and egl-17 animals. These cells initiate migration normally but stop prematurely, approximately half way along their migratory routes (Fig. 2A). In the wild type, the gonad plays a role in positioning the SMs (Thomas et al. 1990; Li and Chalfie, 1990). We tested the effect of altering the position of the gonad on the migration of the SMs in these mutants by constructing double mutants with dig-1 (nl321), a mutation that causes (he anterior displacement of the gonad (Thomas et al. 1990). The final positions of the SMs in the double mutants are displaced anteriorly relative to their positions in the single mutants (P ⩽0.001, Fig. 2B). Moreover, the average distance between the center of the gonad and the final positions of the SMs seen in the single mutants is roughly maintained in the dig-1 double mutants, even though the gonad is displaced anteriorly. These observations suggest that the SMs in egl-15 and egl-17 animals are capable of moving further anteriorly, but stop when they reach a certain distance from the gonad.

To test whether the gonad is responsible for the mispositioning of the SMs in these mutants, the somatic gonadal precursor cells Zl and Z4 (Kimble and Hirsh, 1979; Fig. 3A) were destroyed by laser microsurgery (ablation). When these cells are ablated in the wild type, the migrations of the SMs are, on average, shortened slightly, and the final positions of the SMs span a broader range than in unablated animals (Fig. 3B; Thomas et al. 1990). By contrast, ablation of the somatic gonad in egl-15 and egl-17 animals caused the migrations of the SMs to be significantly lengthened (P ⩽0.000l, Fig. 3C,D). Ablation of Zl and Z4not only destroys the somatic gonad but also prevents the proliferation of the germline (Kimble and White, 1981) and the induction of vulval development (Sulston and White, 1980; Kimble, 1981). To demonstrate that these secondary consequences of the destruction of the somatic gonad were not responsible for altering the positions of the SMs in these mutants, we ablated the germline precursor cells (Z2 and Z3) and the blast cells that give rise to the vulval precursor cells (P3/4, P5/6 and P7/8 on both sides), leaving the somatic gonad intact. The SM migrations in these animals were not rescued to the extent seen after ablation of Z1 and Z4 (P⩽0.007, Fig. 3C,D). Thus, in egl-15 and egl-17 mutants, the somatic gonad plays a major role in causing the premature termination of the SM migrations. The positions of the SMs in these animals are also significantly different (P⩽0.0002) from those in unablated animals. After the ablation of Z2 and Z3, the somatic gonad still grows normally, but, since there are hardly any germline cells, the gonad is not filled to the same extent as is normal. The partial rescue observed after such ablations might reflect the reduced extent of the somatic gonad, therefore causing the effect of the somatic gonad to be diminished.

After ablation of Z1 and Z4, the distribution of the SMs in egl-15 animals is different from that in wild-type animals in which Z1 and Z4 have been ablated (P⩽S0.001, Fig. 3B,C). The positions of the SMs in egl-17 and wild-type animals lacking the somatic gonad are also different, since the average position in egl-17 animals is significantly anterior to that in wild-type animals (P=0.0002, Fig. 3B,D). These results indicate that these egl-15 and egl-17 mutations affect not only the interaction of the SMs with the somatic gonad but also another aspect of the SM migration that does not depend on the gonad. These results also suggest that the egl-15 and egl-17 genes can act outside the gonad. One model that can accomodate the effects of these mutations on both the gonad-dependent and the gonadindependent control of the SM migration is that these genes are required for the proper response of the SMs to multiple signals from other cells.

In wild-type animals, a signal that attracts the SMs to the center of the gonad emanates from four gonadal cells (Zl.pa, Z1 .pp, Z4.aa, Z4.ap) or their descendants (Thomas et al. 1990; see the legend to Fig. 3 for cell nomenclature). To determine if these same cells are responsible for stopping the SM migrations prematurely in egl-15 and egl-17 animals, we killed various descendants of the Z1 and Z4 blast cells by laser ablation in these mutants (Fig. 3C,D). The SM positions after ablation of either Z1 or Z4 alone were not rescued to the same extent as in animals in which both Z1 and Z4 were ablated (P⩽ 0.0l). Thus, in subsequent experiments we ablated the equivalent, symmetrical descendants of both Z1 and Z4 (see Fig. 3A). Ablation of Zl.a/Z4.p did not affect the positions of the SMs, while ablation of Zl.p/Z4.a dramatically reduced the migration defect of these mutants Zl.p/Z4.a or their descendants are primarily responsible for the mispositioning of the SMs in both egl-15 and egl-17 animals.

We then ablated each of the daughters of Zl.p/Z4.a. Ablation of Zl.pp/Z4.aa resulted in some rescue of the SM migration defect (P⩽0.002), suggesting that these cells cause a migration defect in egl-15 and egl-17 mutants. In these Zl.pp/Z4.aa-ablated animals, the SMs migrated anteriorly until they stopped at their final positions, as they do in intact wild-type, egl-15 and egl-17 animals. Ablation of Zl.pa/Z4.ap, the other daughters of Zl.p/Z4.a, also affected the migration of some of the SMs. After ablation of Zl.pa/Z4.ap, not only did some of the SMs migrate to positions far anterior of their final positions in unablated animals, but also some of the SMs migrated to flank the center of the gonad and then reversed direction and moved posteriorly. These results indicate that Zl.pa/Z4.ap also play a role in the SM migration defect in these mutants. Thus, Zl.p/Z4.a cause a significant displacement of the SMs in egl-15 and egl-17 animals, and both daughters appear to contribute to this effect. The cells that are responsible for the premature termination of the SMs in these egl-15 and egl-17 mutants are the same cells that attract the SMs to the center of the gonad in wild-type animals (Thomas et al. 1990).

Two observations suggest that the premature termination of the SM migrations in egl-15 and egl-17 animals might not require direct cell-cell contact between the SMs and the somatic gonad. First, in many animals in which Zl.a/Z4.p have been ablated, the SMs and the gonad appear not to be in direct contact, and yet the SMs stop prematurely. (Zl.a and Z4.p generate the distal tip cells (Kimble and Hirsh, 1979; Fig. 3A), which are essential for the gonad to extend antero-posteriorly (Kimble and White, 1981) and reach the positions at which the SMs are located in the mutants.) Second, the posterior arm of the gonad runs along the left side of the animal and, thus, is in close juxtaposition with only the left SM (Fig. 3A). The right and left SMs are equally posteriorly displaced in egl-15 and egl-17 mutants (data not shown), indicating again that the SM migrations can be terminated in the absence of any obvious contact with the gonad.

Our observations demonstrate that in egl-15 and egl-17 mutants the gonad produces a signal that probably acts at a distance to cause the premature termination of the SM migrations. Since some SMs in Zl.pa/Z4.apablated mutant animals reverse direction if they reach the center of the gonad, these findings suggest that this gonadal signal repels the SMs in egl-15 and egl-17 animals. This signal emanates from the cells Zl.pp, Z4.aa, Zl.pa and Z4.ap or their descendants, which are the same cells that attract the SMs to their final positions in the wild-type animal (Thomas et al. 1990). Thus, it seems likely that the effect of these mutations is to convert the normal attractive interaction between the gonad and the SMs into repulsion.

In these egl-15 and egl-17 mutants, ablation of any of the four signalling cells (Zl.pp, Zl.pa, Z4.aa and Z4.ap; see Fig. 3) or even of some of their descendants (unpublished data) consistently mitigates the SM migration defect, suggesting that the contributions of these cells to the posterior displacement of the SMs is additive. Since the behavior of the SMs in animals in which Zl.pp/Z4.aa have been ablated is different from that in animals in which Zl.pa/Z4.ap have been ablated, these cells might contribute differently to the effect on the SM migrations. One plausible model consistent with the data is that the effect of Zl.pp/Z4.aa is strong and late-acting, while the effect of Zl.pa/Z4.ap is weak and early-acting. In this case, ablation of Zl.pp/Z4.aa would leave only the weak early-acting effect, severely diminishing the migration defect but keeping the SMs posterior of the center of the gonad. By contrast, ablation of Zl.pa/Z4.ap would remove the weak early effect, allowing the SMs initially to migrate without hindrance to the center of the animal. However, the late-acting effect of Zl.pp/Z4.aa would still be present, and, once active, could propel the SMs away from the center of the gonad either anteriorly or posteriorly.

The mechanism by which these recessive egl-15 and egl-17 mutations reverse the sign of the normal interaction between the gonad and the SMs is not known. Three aspects of this interaction could be affected by these mutations: the signal, the reception and transduction of the signal, and the mechanics of movement. In the first case, the signal itself could be changed by the mutation, for example, by creating a novel repellant. In the second case, the mutation could alter how the signal is sensed. For example, if the normal gonadal signal can activate two opposing response systems, one that causes attraction and one that causes repulsion, these mutations could enhance the repulsion relative to the attraction. Such a mechanism has been proposed to be responsible for the phenotype of the Paramecium tetraurelia d4-530 mutant, which is repelled by rather than attracted to sodium acetate (Van Houten, 1977, 1979), and for the phenotype of the Drosophila melanogaster Photophobe mutant, which is repelled by rather than attracted to green fight (Ballinger and Benzer, 1988). We suspected that the gonad might have a latent capability to repel the SMs, since the homologous SMs in the male migrate posteriorly during wild-type development (Sulston and Horvitz, 1977). Thus, male SMs might be repelled by the gonad, and egl-15 and egl-17 mutations might cause this male-specific repulsion to occur inappropriately in hermaphrodites. However, ablation of the somatic gonad in wild-type males did not prevent or reverse the posterior migration of the male SMs (data not shown), so we have no evidence that the gonad repels the SMs in males. In the-third case, these mutations might alter structural components involved in the mechanics of cell movement. Flagellar motor components are thought to be affected in certain bacterial chemotaxis mutants repelled by compounds that are normally attractive (Rubik and Koshland, 1978; Kahn et al. 1978; Kuo and Koshland, 1986).

A variety of mechanisms, including chemotáxis and differential adhesiveness, are thought to control the directional migration of cells in various organisms (Singer and Kupfer, 1986; Erickson, 1990; Keynes and Cook, 1990). In C. elegans, a number of genes that play roles in other cell migrations have been identified (Chalfie et al. 1983; Kenyon, 1986; Hedgecock et al. 1987; Desai et al. 1988; Manser and Wood, 1990). Some of these genes have been postulated to affect adhesive gradients that guide dorsal/ventral movements of cells and axonal processes (Hedgecock et al. 1990). Since a major component of the SM migration is independent of the gonadal signal, similar anterior/posterior adhesive gradients might help guide the SM migration. However, this migration is also controlled by the longdistance interaction between the gonad and the SMs. Long-range signalling is known to be important in directing both cell movement and axonal outgrowth (Erikson, 1990; Dodd and Jessell, 1988; Trinkhaus, 1984). The identification of egl-15 and egl-17 as functioning within a system of cell-cell signalling between the gonad and the SMs should help reveal the molecular mechanisms tfiat cause cells to assume their appropriate positions during animal development.

We thank D. Miller for the anti-myosin antibody, and J. Kimble, C. Donnelly, S. Gottlieb and many members of our laboratory for comments concerning the manuscript. This work was supported by research grant GM24663 from the US Public Health Service to H.R.H. and by postdoctoral fellowship PF-1200 from the American Cancer Society to M.J.S. H.R.H. is an Investigator and M.J.S. is a Research Associate of the Howard Hughes Medical Institute.

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