Notch-head worms have been known since Sydney Brenner isolated
vab-1(
e2) in October 1967, but the exact nature and cause of this bizarre phenotype is as yet unknown. Notched worms have deranged head morphology: in all mutants giving this phenotype the disruption is very variable, ranging from a slight displacement of the buccal cavity to what appear to be almost two-headed worms. Morphology is almost always worse ventrally. Highly penetrant Notch mutations have been found for the three loci
vab-1 II,
vab-2 IV, and
vab-3 X; The phenotypes of
vab-1 and
vab-2 mutants are very similar, while
vab-3 mutants exhibit amusing pleiotropies. In the hope that the Notch mutants will provide clues to the embryonic morphogenesis of the head, I have taken a closer look at them, starting with
vab-3.The two previously described alleles of
vab-3(
e648,
e1062) appear intermediate in strength, based on penetrance.
e41,
e1022 and
e1178 were found lurking in the e list;
e1178 is the strongest allele known (60% of a brood die as larvae, apparently because the worms cannot take in food).
e2429 is a weak allele found in an outcross of an unrelated mutant. By chance, I noticed that the gonad in
vab-3 hermaphrodites is abnormal, as a result of a distal tip cell migration defect. This Mig is similar to that described by Hedgecock for
lin-20(
e1796).
vab-3 and
e1796 map to the same region on XR, and indeed
e1796 fails to complement stronger
vab-3 alleles for the Mig phenotype, although it complements them for Vab. All the above alleles are assigned to
vab-3 by similarity of phenotype and failure of
e1796 to complement for Mig. The Mig in strong alleles is fully penetrant, but does not seem more severe than in
e1796. Thus,
e1796 appears to be a hypomorphic allele of
vab-3.The other phenotype described for
e1796 is that the lineages of postembryonic head blast cells are abnormal, in some cases transformed to those of posterior homologues (Hedgecock, TINS 1985). A preliminary check of
e2429 and
e648 showed that similar lineage alterations occur in these mutants. In wild-type and
e1796, the alae fade out anteriorly between the pharyngeal bulbs, but in strong
vab-3 mutants they continue up to the tip (if there is one), or may pass through the notch to link up with the alae on the other side of the worm; this may suggest a stronger transformation of H0 and H1 terminal fates. The head defects in
vab-3 worms arise during embryonic development. To learn more about their cause, I have started looking at the embryonic lineages of
vab-3(
e1178) using John White's 4-D microscope. In one embryo the lineages of the H cells were normal.
vab-3 males cannot mate, as a result of abnormal internal blast cell lineages. Helen Chamberlin (p.c.) has studied the male tail lineages in
e648 and another putative
vab-3 allele,
sy66. In these males and one
e2429 male lineaged, the B and Y lineages were abnormal: the defects could be interpreted as partial transformations of the fates of B.al/r to B.p and Y.pl/r to Y.a.
e1796 male tails appear wild-type internally, although they have a 'Sixless' ray defect (Baird and Emmons, WBG 11.2,
p116). Since none of the stronger alleles has any fan defect, this may be due to a second mutation in the strain (
mab-18 maps nearby on X). The pleiotropies of
vab-3 mutants await convincing explanation. The Notch may be a result of abnormal embryonic cell migrations; perhaps only mutations weakly affecting this process will be viable, hence the variability.