Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos

Michael J. Parsons, Isabel Campos, Elizabeth M A Hirst, Derek L. Stemple

Research output: Contribution to journalArticle

Abstract

Muscular dystrophy is frequently caused by disruption of the dystrophin-glycoprotein complex (DGC), which links muscle cells to the extracellular matrix. Dystroglycan, a central component of the DGC, serves as a laminin receptor via its extracellular α subunit, and interacts with dystrophin (and thus the actin cytoskeleton) through its integral membrane β subunit. We have removed the function of dystroglycan in zebrafish embryos. In contrast to mouse, where dystroglycan mutations lead to peri-implantation lethality, dystroglycan is dispensable for basement membrane formation during early zebrafish development. At later stages, however, loss of dystroglycan leads to a disruption of the DGC, concurrent with loss of muscle integrity and necrosis. In addition, we find that loss of the DGC leads to loss of sarcomere and sarcoplasmic reticulum organisation. The DGC is required for long-term survival of muscle cells in zebrafish, but is dispensable for muscle formation. Dystroglycan or the DGC is also required for normal sarcomere and sarcoplasmic reticulum organisation. Because zebrafish embryos lacking dystroglycan share several characteristics with human muscular dystrophy, they should serve as a useful model for the disease. In addition, knowing the dystroglycan null phenotype in zebrafish will facilitate the isolation of other molecules involved in muscular dystrophy pathogenesis.

Original languageEnglish (US)
Pages (from-to)3505-3512
Number of pages8
JournalDevelopment
Volume129
Issue number14
StatePublished - Jul 2002
Externally publishedYes

Fingerprint

Dystroglycans
Muscular Dystrophies
Dystrophin
Zebrafish
Embryonic Structures
Glycoproteins
Sarcomeres
Sarcoplasmic Reticulum
Muscle Cells
Laminin Receptors
Muscles
Actin Cytoskeleton
Basement Membrane
Extracellular Matrix
Necrosis
Phenotype
Mutation
Membranes

Keywords

  • Danio rerio
  • Dystronglycan
  • Dystrophin
  • Muscular dystrophy
  • Sarcomere
  • Sarcoplasmic reticulum
  • Zebrafish

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Parsons, M. J., Campos, I., Hirst, E. M. A., & Stemple, D. L. (2002). Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos. Development, 129(14), 3505-3512.

Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos. / Parsons, Michael J.; Campos, Isabel; Hirst, Elizabeth M A; Stemple, Derek L.

In: Development, Vol. 129, No. 14, 07.2002, p. 3505-3512.

Research output: Contribution to journalArticle

Parsons, MJ, Campos, I, Hirst, EMA & Stemple, DL 2002, 'Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos', Development, vol. 129, no. 14, pp. 3505-3512.
Parsons MJ, Campos I, Hirst EMA, Stemple DL. Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos. Development. 2002 Jul;129(14):3505-3512.
Parsons, Michael J. ; Campos, Isabel ; Hirst, Elizabeth M A ; Stemple, Derek L. / Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos. In: Development. 2002 ; Vol. 129, No. 14. pp. 3505-3512.
@article{705346de061145318ccb956bdd2d3704,
title = "Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos",
abstract = "Muscular dystrophy is frequently caused by disruption of the dystrophin-glycoprotein complex (DGC), which links muscle cells to the extracellular matrix. Dystroglycan, a central component of the DGC, serves as a laminin receptor via its extracellular α subunit, and interacts with dystrophin (and thus the actin cytoskeleton) through its integral membrane β subunit. We have removed the function of dystroglycan in zebrafish embryos. In contrast to mouse, where dystroglycan mutations lead to peri-implantation lethality, dystroglycan is dispensable for basement membrane formation during early zebrafish development. At later stages, however, loss of dystroglycan leads to a disruption of the DGC, concurrent with loss of muscle integrity and necrosis. In addition, we find that loss of the DGC leads to loss of sarcomere and sarcoplasmic reticulum organisation. The DGC is required for long-term survival of muscle cells in zebrafish, but is dispensable for muscle formation. Dystroglycan or the DGC is also required for normal sarcomere and sarcoplasmic reticulum organisation. Because zebrafish embryos lacking dystroglycan share several characteristics with human muscular dystrophy, they should serve as a useful model for the disease. In addition, knowing the dystroglycan null phenotype in zebrafish will facilitate the isolation of other molecules involved in muscular dystrophy pathogenesis.",
keywords = "Danio rerio, Dystronglycan, Dystrophin, Muscular dystrophy, Sarcomere, Sarcoplasmic reticulum, Zebrafish",
author = "Parsons, {Michael J.} and Isabel Campos and Hirst, {Elizabeth M A} and Stemple, {Derek L.}",
year = "2002",
month = "7",
language = "English (US)",
volume = "129",
pages = "3505--3512",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "14",

}

TY - JOUR

T1 - Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos

AU - Parsons, Michael J.

AU - Campos, Isabel

AU - Hirst, Elizabeth M A

AU - Stemple, Derek L.

PY - 2002/7

Y1 - 2002/7

N2 - Muscular dystrophy is frequently caused by disruption of the dystrophin-glycoprotein complex (DGC), which links muscle cells to the extracellular matrix. Dystroglycan, a central component of the DGC, serves as a laminin receptor via its extracellular α subunit, and interacts with dystrophin (and thus the actin cytoskeleton) through its integral membrane β subunit. We have removed the function of dystroglycan in zebrafish embryos. In contrast to mouse, where dystroglycan mutations lead to peri-implantation lethality, dystroglycan is dispensable for basement membrane formation during early zebrafish development. At later stages, however, loss of dystroglycan leads to a disruption of the DGC, concurrent with loss of muscle integrity and necrosis. In addition, we find that loss of the DGC leads to loss of sarcomere and sarcoplasmic reticulum organisation. The DGC is required for long-term survival of muscle cells in zebrafish, but is dispensable for muscle formation. Dystroglycan or the DGC is also required for normal sarcomere and sarcoplasmic reticulum organisation. Because zebrafish embryos lacking dystroglycan share several characteristics with human muscular dystrophy, they should serve as a useful model for the disease. In addition, knowing the dystroglycan null phenotype in zebrafish will facilitate the isolation of other molecules involved in muscular dystrophy pathogenesis.

AB - Muscular dystrophy is frequently caused by disruption of the dystrophin-glycoprotein complex (DGC), which links muscle cells to the extracellular matrix. Dystroglycan, a central component of the DGC, serves as a laminin receptor via its extracellular α subunit, and interacts with dystrophin (and thus the actin cytoskeleton) through its integral membrane β subunit. We have removed the function of dystroglycan in zebrafish embryos. In contrast to mouse, where dystroglycan mutations lead to peri-implantation lethality, dystroglycan is dispensable for basement membrane formation during early zebrafish development. At later stages, however, loss of dystroglycan leads to a disruption of the DGC, concurrent with loss of muscle integrity and necrosis. In addition, we find that loss of the DGC leads to loss of sarcomere and sarcoplasmic reticulum organisation. The DGC is required for long-term survival of muscle cells in zebrafish, but is dispensable for muscle formation. Dystroglycan or the DGC is also required for normal sarcomere and sarcoplasmic reticulum organisation. Because zebrafish embryos lacking dystroglycan share several characteristics with human muscular dystrophy, they should serve as a useful model for the disease. In addition, knowing the dystroglycan null phenotype in zebrafish will facilitate the isolation of other molecules involved in muscular dystrophy pathogenesis.

KW - Danio rerio

KW - Dystronglycan

KW - Dystrophin

KW - Muscular dystrophy

KW - Sarcomere

KW - Sarcoplasmic reticulum

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=0036637659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036637659&partnerID=8YFLogxK

M3 - Article

VL - 129

SP - 3505

EP - 3512

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 14

ER -