Worm Breeder's Gazette 11(4): 95
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.
Neurons and muscles adhere to the hypodermis via contacts with the basolateral cell membranes or basal lamina, respectively. For stronger anchorage, many cells induce assembly of transhypodermal cytoskeletal elements, generally intermediate filaments (IFs), that couple them mechanically to the cuticle(1). In him-4 mutants, trans-hypodermal anchorage of diverse cell types is defective. e1266 and e1267, isolated by D. Riddle following ICR mutagenesis, and rh166, obtained by EMS mutagenesis, all share three, seemingly unrelated, phenotypes: (1) elevated meiotic nondisjunction of the X chromosome (Him phenotype), (2) abnormal linker cell migration (Mig phenotype), and (3) defective static attachment of cells to the body wall. The Him defect is comparable in all three strains: hermaphrodites have about 5% males among their self-progeny ( 2). In mutant males, the linker cell often fails to reflex and instead continues anterior along the ventral muscles or hypodermis onto the head (2,3). This phene occurs in about 60% of e1267 males but only 30% of rh166 males (Figure 1). In the remaining males, the migration is normal until approaching the cloaca; there the linker cell may slow and stop before connecting. Premature stopping is more frequent in e1267 (perhaps 100% penetrant) than rh166 males (about 50%). The Mig phenotype explains why e1267 males are sterile, i.e., the vas deferens is never joined to the cloaca; if this is the sole cause, then some 30% of rh166 males should prove fertile. In wild type males, the distal gonad does not elongate during larval growth; in mutants, the distal arm often meanders posteriorly during L4 stage. This is not an active migration led by the distal tip cell but passive extension resulting from germ cell proliferation. Distal extension is not simply the result of removing the steric hindrance provided by the reflexed proximal gonad; this phene is not observed in mig-7 males with failed linker cell reflexion. Wildtype ALM/PLM axons are anchored via the chain: neuronal membrane - extracellular mantle - hypodermal basolateral membrane - IF structure - hypodermal apical membrane - cuticle (Figure 2). The mantle may be a hypodermal secretion induced by neuronal contact; the IF structure is a double track of IF proteins induced by the overlying axon. In mec-1 mutants, both mantle and IFs are absent; axons float unanchored on the hypodermis and are functionless (4). In him-4 mutants, mantle is present as judged by peanut lectin staining but the IF structure is probably absent; axons float on the hypodermis. Unlike mec-1, these mutants are not overtly touch insensitive. In late L4 hermaphrodites, certain uterine (use), vulval (type E), and muscle cells (vm1, um1) attach to the seam syncytium as an orderly complex (5,6). These cells induce tonofilaments in the hypodermis that anchor them to the cuticle (see Wood (1988) Fig. 20, p.116). An outline of the vulval-uterine-seam attachment complex, probably corresponding to the use-seam limits, can be discerned by Nomarski microscopy as a thin-line with down turned ends running through seam cells V3.ppppp and V4.pappp. In him-4 adults, the uterus often everts through the vulva. The use-seam attachment is incomplete or absent in these mutants; vulval E cells still form some attachment to the seam. The rectum sometimes everts during molts, killing him-4 larvae; the cellular mechanism is not known. Gaps between body muscle, possibly a weak mua phenotype, are seen occasionally. Several of the him-4 phenotypes would be lethal if more expressive or penetrant: (1) hermaphrodite broods are small because uterine eversion kills the young adults, (2) the rectum sometimes everts during molts, (3) gaps between body muscles, possibly a weak mua phenotype, have been seen very occasionally. Thus him-4 affects essential events and may itself be an essential gene. A primary defect in the assembly of trans- hypodermal IF anchorages could explain most cellular phenotypes. Dynamic IF structures are also present in the nucleus and might conceivably affect chromosome segregation. Understanding the relation of the Him, Mig, and Mua-like phenotypes may require a biochemical understanding of the him-4 product. [See Figure 1]