Over 30 Caenorhabditis elegans mutants were identified with normal muscle differentiation and initial locomotion followed by catastrophic detachment of skeletal muscles from the body wall. Reducing the strength of muscle contraction in these mutants with a myosin gene mutation suppresses muscle detachment. These dystrophic mutants identify a novel class of genes required for growth and maintenance of functional muscle attachments, not exceptional alleles of genes required for muscle differentiation and contractility. Nine new genes, named mua, and two previously published loci, unc-23 and vab-10, cause fragile musscle attachments. The primary sites of muscle detachment, including the plane of tissue separation, are characteristic for each gene. We suggest these genes identify feedback mechanisms whereby local strain regulates the extent of myofibril contraction and the placement of new muscle attachments in functioning muscles. Finally, we draw some comparisons to vertebrate skin fragility diseases and muscular dystrophies.
REFERENCES
Achanzar
W. E.
, Ward
S.
(1997
) A nematode gene required for sperm vesicle fusion.
J. Cell Sci
110
, 1073
–1081
Andra
K.
, Lassmann
H.
, Bittner
R.
, Shorny
S.
, Fassler
R.
, Propst
F.
, Wiche
G.
(1997
) Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture.
Genes Dev
11
, 3143
–3156
Bashir
R.
, Britton
S.
, Stachan
T.
, Keers
S.
, Vafiadaki
E.
, Lako
M.
, Richard
I.
, Marchand
S.
, Bourg
N.
, Argov
Z.
(1998
) A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B.
Nat. Genet
20
, 37
–42
Berthier
C.
, Blaineau
S.
(1997
) Supramolecular organization of the subsarcolemmal cytoskeleton of adult skeletal muscle fibers. A review. Biol.
Cell
89
, 413
–434
Bogaert
T.
, Goh
P. Y.
(1991
) Positioning and maintenance of embryonic body wall muscle attachments in C. elegans requires the mup-1 gene.
Development
111
, 667
–681
Bonne
G.
, Di Barletta
M. R.
, Varnous
S.
, Becane
H. M.
, Hammouda
E. H.
, Merlini
L.
, Muntoni
F.
, Greenberg
C. R.
, Urtizberea
J. A.
, Duboc
D.
(1999
) Mutations in the gene encoding lamin A/C couse autosomal dominant Emery-Dreifuss muscular dystrophy.
Nat. Genet
21
, 285
–288
Brais
B.
, Bouchard
J. P.
, Xie
Y. G.
, Rochefort
D. L.
, Chretien
N.
, Tome
F. M.
, Lafreniere
R. G.
, Rommens
J. M.
, Uyama
E.
, Nohira
O.
(1998
) Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy.
Nat. Genet
18
, 164
–167
Brenner
S.
(1974
) The genetics of Caenorhabditis elegans.
Genetics
77
, 71
–94
Brown
S. C.
, Lucy
J. A.
(1993
) Dystrophin as a mechochemical transducer in skeletal muscles.
BioEssays
15
, 413
–419
Bucher
E. A.
, Greenwald
I. S.
(1991
) A genetic mosaic screen of essential zygotic genes in Caenorhabditis elegans.
Genetics
128
, 281
–292
Campbell
K. P.
(1995
) Three muscular dystrophies: loss of cytoskeletal-extracellular matrix linkage.
Cell
80
, 675
–679
Durbeej
M.
, Henry
M. D.
, Campbell
K. P.
(1998
) Dystroglycan in development and disease.
Curr. Opin. Cell Biol
10
, 594
–601
Ellis
J. A.
, Craxton
M.
, Yates
J. R.
, Kendrick-Jones
J.
(1998
) Aberrant intracellular targeting and cell cycle-dependent phosphorylation of emerin contribute to the Emery-Dreifuss muscular dystrophy phenotype.
J. Cell Sci
111
, 781
–792
Epstein
E. H.
(1992
) Molecular genetics of epidermolysis bullosa.
Science
256
, 799
–804
Epstein
H. F.
, Waterston
R. H.
, Brenner
S.
(1974
) A mutant affecting the heavy chain of myosin in C. elegans.
J. Mol. Biol
90
, 291
–300
Francis
G. R.
, Waterston
R. H.
(1985
) Muscle organization in Caenorhabditis elegans: localization of proteins implicated in thin filament attachment and I-band organization.
J. Cell Biol
101
, 1532
–1549
Fuchs
E.
, Cleveland
D. W.
(1998
) A structural scaffolding of intermediate filaments in health and disease.
Science
279
, 514
–519
Hall
D. H.
, Hedgecock
E. M.
(1991
) Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans.
Cell
65
, 837
–847
Hodgkin
J.
, Papp
A.
, Pulak
R.
, Ambros
V.
, Anderson
P.
(1989
) A new class of information supression in the nematode Caenorhabditis elegans.
Genetics
123
, 301
–313
Hodgkin
J.
(1983
) Male phenotypes and mating efficiency in C. elegans.
Genetics
103
, 43
–64
Horvitz
H. R.
, Brenner
S.
, Hodgkin
J.
, Herman
R. K.
(1979
) A uniform genetic nomenclature for the nematode C. elegans.
Mol. Gen. Genetics
175
, 129
–133
Hresko
M. C.
, Williams
B. D.
, Waterston
R. H.
(1994
) Assembly of body wall muscle and muscle cell attachment structures in Caenorhabditis elegans.
J. Cell Bio
124
, 491
–506
Kobayashi
K.
, Nakahori
Y.
, Miyake
M.
, Matsumura
K.
, Kondo-Iida
E.
, Nomura
Y.
, Segawa
M.
, Yoshioka
M.
, Saito
K.
, Osawa
M.
(1998
) An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.
Nature
394
, 388
–392
Law
D. J.
, Tidball
J. G.
(1992
) Dystrophin deficiency is associated with myotendinous junction defects in prenecrotic and fully regenerated skeletal muscle.
Am. J. Pathol
142
, 1513
–1523
Mackenzie
J. M.
Jr, Garcea
R. L.
, Zengel
J. M.
, Epstein
H. F.
(1978
) Muscle development in Caenorhabditis elegans: mutants exhibiting retarded sarcomere construction.
Cell
15
, 751
–762
McLean
W. H.
, Pulkkinen
L.
, Smith
F. J.
, Rugg
E. L.
, Lane
E. B.
, Bullrich
F.
, Burgeson
R. E.
, Amano
S.
, Hudson
D. L.
, Owaribe
K.
(1996
) Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization.
Genes Dev
10
, 1724
–1735
Meneely
P. M.
, Herman
R. K.
(1981
) Suppression and function of X-linked lethal and sterile mutations in Caenorhabditis elegans.
Genetics
97
, 65
–84
Moerman
D. G.
, Hutter
H.
, Mullen
G. P.
, Schnabel
R.
(1996
) Cell autonomous expression of perlecan and plasticity of cell shape in embryonic muscle of Caenorhabditis elegans.
Dev. Biol
173
, 228
–242
Okkema
P. G.
, Fire
A.
(1994
) The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle.
Development
120
, 2175
–2186
Ozawa
E.
, Noguchi
S.
, Mizuno
Y.
, Hagiwara
Y.
, Yoshida
M.
(1998
) From dystrophinopathy to sarcoglycanopathy: evolution of a concept of muscular dystrophy.
Muscle Nerve
21
, 421
–438
Petrof
B. J.
(1998
) The molecular basis of activity-induced muscle injury in Duchenne muscular dystrophy.
Mol. Cell Biochem
179
, 111
–123
Richard
I.
, Broux
O.
, Allamand
V.
, Fougerousse
F.
, Chiannilkulchai
N.
, Bourg
N.
, Breguler
L.
, Devaud
C.
, Pasturuad
P.
, Roudaut
C.
(1995
) Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.
Cell
81
, 27
–40
Rogalski
T. M.
, Williams
B. D.
, Mullen
G. P.
, Moerman
D. G.
(1993
) Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan.
Genes Dev
7
, 1471
–1484
White
J. G.
, Southgate
E.
, Thomson
J. N.
, Brenner
S.
(1976
) The structure of the ventral nerve cord of C. elegans.
Phil. Trans. R. Soc. (London)
275
, 327
–348
Williams
B. D.
, Waterston
R. H.
(1994
) Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations.
J. Cell Biol
124
, 475
–490
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