Worm Breeder's Gazette 9(2): 59

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Changing the Position of the Gonad Alters Vulval Cell Fates, Muscle Cell Migration, and the Position of Synapse Forrmation by the HSN Neurons

J. Thomas and B. Horvitz

From a screen (after EMS mutagenesis) for animals with 
morphologically abnormal gonads, we have isolated the mutation n1321.  
Mutants homozygous for n1321 have a fertile gonad of apparently normal 
morphology that is usually displaced to a position considerably 
anterior of normal.  We have nicknamed this phenotype 'egghead' (Egh), 
since the eggs in the adult are shifted toward the head.  In most 
n1321 L1 animals, the gonad primordium is located somewhat anterior of 
normal (with respect to the V and P cells and other body markers) and 
is in a ventral position (as in N2).  In about 10% of the animals (at 
20 C), the gonad primordium is located dorsally, separated from the 
ventral cord and hypodermis by the intestine.  During postembryonic 
development the center of the gonad remains in whatever position it 
occupied in the L1.  The gene defined by n1321 lies in the cluster on 
chromosome III in the deficiency interval covered by nDf16 but not 
nDf20.  The Egh and dorsal gonad phenotypes of n1321 are recessive, 
but the mutation appears not to be null, because the position of the 
gonad primordium is shifted even further anterior in animals of 
genotype n1321/nDf16.
We have identified three other developmental abnormalities in n1321 
animals.  All of these defects are apparently caused by the 
displacement of the gonad.  First, the cells of the vulval equivalence 
group P(3-8).p can be altered in fate in a manner dependent on the 
position of the gonad (the gonad is required for the induction of 
vulval cell lineages in N2).  Second, the sex myoblasts, which 
generate the vulval and uterine muscles that control egg laying, 
migrate further anterior than in the wild type, to a position 
determined by the displaced gonad.  Third, the HSN neurons, which 
innervate the vulval muscles and drive egg-laying, have normally 
positioned cell bodies but appear to innervate the displaced vulval 
muscles, suggesting that their processes extend further anterior than 
normal before making synapses with the muscle cells.  It is 
interesting to note that these three developmental alterations are 
precisely those necessary to ensure that an animal with a displaced 
gonad will be egg-laying proficient.  The observations that have led 
to these conclusions are discussed below.
1.  In many n1321 animals in which the gonad was mispositioned, the 
vulval cell lineages were generated by the three P(3-8).p cells 
located nearest the anchor cell (which is generated postembryonically 
within the somatic gonad and induces the vulval cell lineages in N2).  
For example, in several n1321 animals the vulva was formed from P(3-5).
p, whereas in N2 it is formed from P(5-7).p.  Induction of vulval 
lineages in n1321 animals is anchor cell dependent in cases of both 
ventrally and dorsally located gonads, since no vulval lineages were 
induced in 4/4 animals in which the gonad was ablated at the L1 stage (
two ventral and two dorsal gonads), and no vulval lineages are induced 
in animals of genotype n1321 lin-12(n302) (the gonads of which lack an 
anchor cell as a result of the lin-12 mutation).  We conclude that the 
location of the anchor cell determines which cells of the vulval 
equivalence group will undergo vulval cell lineages.  These 
observations support earlier conclusions reached by Paul Sternberg.
The anchor cell can induce normal vulval cell lineages by P(3-8).p 
even when located dorsally, separated from them by about half the body 
width.  In about 2/3 of the animals with a dorsally located gonad 
between one and four P(3-8).p cells are induced to undergo vulval 
lineages.  Since the anchor cell is clearly not in contact with its 
target Pn.p cells at any time in these animals, this result means that 
the signal for induction of the vulval lineages is diffusible.  A 
diffusible anchor cell signal is an important aspect of the model of 
Sternberg and Horvitz (Cell 44: 761-772, 1986) that determination of 
the vulval cell lineages occurs via a graded anchor cell signal.  
Since the gradation of the anchor cell signal should be altered in 
animals with a dorsally located anchor cell, we may be able to use 
n1321 to further test this model.
2.  The migration of the hermaphrodite sex myoblasts (SMs) is 
altered in n1321 animals.  Normally the two bilateral SMs migrate 
during the L2 stage from a posterior position to a position directly 
lateral to the middle of the developing gonad, and there undergo three 
rounds of division to generate the sex muscles.  Several observations 
support a role for the gonad in determining the SM migration.  First, 
the SMs in n1321 animals extend their migration further anterior than 
normal and stop when located directly lateral to the middle of the 
displaced gonad.  Second, when the gonad is located dorsally the SMs 
migrate anteriorly along their normal ventral route but then turn and 
move dorsally when they have reached the midpoint of the gonad.  Third,
when the gonad primordium is ablated in the early L1 in either N2 or 
n1321 animals, the SMs migrate anteriorly as usual but stop in a 
variable position usually near, but rarely exactly at, the normal N2 
position.  The simplest explanation of these results is that the SMs 
themselves determine the direction and approximate extent of their 
migration, but a signal generated in the gonad determines their final 
position more precisely.
Ablation of the germ line precursors Z2 and Z3 has no effect on the 
migration of the SMs in either N2 or n1321.  However ablation of the 
somatic gonadal precursor cells Z1 and Z4 results in the 
characteristic migration defect described above.  We conclude that the 
somatic but not the germ line gonad is required for the generation of 
the signal that directs the SM migration.
3.  The embryonic migration of the HSN cell body is unaffected in 
n1321 animals (the HSN is located in the wild-type position with 
respect to the body).  This observation means that the sex muscles 
that it normally innervates are abnormally far away anteriorly.  
Nevertheless, of eight young adult n1321 animals with vulvae that were 
displaced well anterior of normal, only one later became severely egg-
laying defective (as is characteristic of animals lacking HSN function)
.  This result suggests that in seven of eight animals at least one 
HSN neuron properly innervated the sex muscles and could drive egg-
laying.  We infer that an HSN neuron can grow to its muscle targets 
and make proper synaptic connections even when its cell body is much 
further than normal from its target.