| Summary: | Myogenesis in Caenorhabditis elegans is composed of several stages: the generation of
presumptive myoblasts; the migration of these cells dorsally and ventrally from their
lateral position to form the muscle quadrants; the accumulation of muscle specific
proteins in these cells; the polarization of the cells; and, finally, the organization of
sarcomeres and attachment structures within the cells. The goal of this thesis work has
been to identify genes involved in this process. From a mutant screen designed to
identify mutations that disrupt muscle development during C. elegans embryogenesis,
eight mutations have been isolated and placed into five distinct classes.
Two of the mutants identified in this screen have been characterized in greater detail and
the affected genes have been cloned. One of the mutants, let-268 (a class IV mutant),
encodes a procollagen processing enzyme, procollagen lysyl hydroxylase, required for
post-translational modifications of collagen. In let-268 mutants the processing and
secretion of type IV collagen is disrupted. An examination of the body wall muscle in
these mutant animals reveals normal myofilament assembly prior to contraction.
However, once body wall muscle contraction commences the muscle cells separate from
the underlying epidermal layer (hypodermis) and the myofilaments become disorganized.
These observations indicate that type IV collagen is required in the basement membrane
for mechanical support and not for organogenesis of the body wall muscle. The other
mutant examined in greater detail is spc-1 (class V mutant), spc-1 encodes the only α
spectrin gene in the C. elegans genome. Animals lacking functional α spectrin die just after hatching and have defects in myofilament organization. More specifically, when
compared to myofilaments in wild type animals, the myofilaments in the mutant animals
are abnormally oriented relative to the longitudinal axis of the embryo. In cross section,
the myofilaments appear to be loosely associated with the sarcolemma as compared to
wild type. In addition, analysis of the basement membrane and the hypodermis of spc-1(ra409) mutants provides evidence that the body wall muscle directs where the
basement membrane is established and signals the hypodermis to determine where
muscle anchoring structures are assembled in this tissue. === Science, Faculty of === Zoology, Department of === Graduate
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