Worm Breeder's Gazette 14(1): 72 (October 1, 1995)

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.

hmp-1 Encodes an Alpha-catenin Required for Morphogenesis of the Embryo

Mike Costa1, Bill Raich2, Jeff Hardin2, Jim Priess3

1 Div. of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2 Cell and Molecular Biology, Univ. of Wisconsin, Madison, WI 53706
3 Div. of Basic Sciences, Fred Hutchinson Cancer Research Center and HHMI, Seattle, WA 98109

Cell movements and shape changes of the hypodermal cells during
embryogenesis in C. elegans appear to drive morphogenesis of the body.
At about 200 min of development, the hypodermal cells initially located
on the dorsal surface of the embryo extend ventrally and anteriorly.
Thus the embryo becomes enclosed in a monolayer of hypodermal cells that
are linked to each other by adherens junctions.  Immediately following
hypodermal enclosure, the hypodermal cells begin to shorten along the
circumferential direction and lengthen in the longitudinal
(anteroposterior) dimension as the entire embryo elongates approximately
four-fold.  Circumferential actin filament bundles form in all five rows
of hypodermal cells (one dorsal, two lateral, and two ventral) at the
start of elongation and appear to contract to generate the force that
transforms the shapes of the hypodermal cells and the embryo.

We have isolated several zygotic lethal mutations in a gene named hmp-1
(humpback) that seem to specifically block elongation of the embryo.
hmp-1 mutants form the normal pattern of hypodermal cells but arrest
elongation at an early stage (1.25- to 1.5-fold) and develop abnormal
lumps in the dorsal hypodermis.  Analysis of a genetic deficiency
indicates that this phenotype results from complete loss of zygotic gene
function.  Curiously, the primary defect in hmp-1 embryos appears to be
failure of the dorsal hypodermis to elongate.  The ventral (and possibly
also lateral) hypodermis elongates initially, presumably forcing the
dorsal hypodermis into ectopic folds.  Circumferential actin filament
bundles form properly in the hypodermal cells of hmp-1 embryos.
However, at the start of elongation, the filaments in the dorsal
hypodermis pull away from the adherens junctions where they normally
remain anchored.

We positioned the hmp-1 mutations with respect to the physical map and
obtained transgenic rescue with cosmid DNA.  Analysis of cDNA clones in
this region from the genome sequencing project revealed that one cDNA
hybridized to the rescuing cosmid.  Injection of anti-sense RNA made
from this cDNA into the gonads of wild-type animals produces the Hmp-1
phenotype in embryos, indicating that this cDNA encodes hmp-1.
Extending Y. Kohara's initial sequence of this clone, we find that it
appears to be a partial cDNA encoding the C-terminal one-third of an
a-catenin homologue (52% identical to Drosophila a-catenin).  a-catenin
is a component of vertebrate adherens junctions that binds to the
cytoplasmic side of cadherins (transmembrane, homotypic cell adhesion
proteins) and to F-actin.  Our mutant analysis suggests that, in some
cells, a-catenin is required to anchor actin filaments at adherens
junctions and transmit force from the cytoskeleton to the membrane, and
ultimately to neighboring cells.

hmp-1 RNA is expressed zygotically in all hypodermal cells before
hypodermal enclosure of the embryo.  Zygotic expression is also observed
in the developing intestine and pharynx, tissues containing adherens
junctions.  In addition, hmp-1 RNA is expressed maternally and present
in all early blastomeres.  We have begun to examine phenotypes of
embryos lacking both maternal and zygotic hmp-1 gene activity using
germline mutant clones and transgenic strains.  In these embryos, the
hypodermis fails to fully enclose the anterior and ventral regions,
possibly due to defects in cell adhesion or migration.  The intestine
also shows defects that might possibly result from defective cell

We thank Andreas Wissmann for providing one of the hmp-1 alleles.