We report that the Drosophila mind bomb2 (mib2) gene is a novel regulator of muscle development. Unlike its paralogue, mib1, zygotic expression of mib2 is restricted to somatic and visceral muscle progenitors, and their respective differentiated musculatures. We demonstrate that in embryos that lack functional Mib2, muscle detachment is observed beginning in mid stage 15 and progresses rapidly, culminating in catastrophic degeneration and loss of most somatic muscles by stage 17. Notably, the degenerating muscles are positive for apoptosis markers, and inhibition of apoptosis in muscles prevents to a significant degree the muscle defects. Rescue experiments with Mib1 and Neuralized show further that these E3 ubiquitin ligases are not capable of ameliorating the muscle mutant phenotype of mib2. Our data suggest strongly that mib2 is involved in a novel Notch- and integrin-independent pathway that maintains the integrity of fully differentiated muscles and prevents their apoptotic degeneration.
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22 October 2007
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October 22 2007
Drosophila mind bomb2 is required for maintaining muscle integrity and survival
Hanh T. Nguyen,
Hanh T. Nguyen
1Department of Medicine (Division of Cardiology), and Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, Bronx, NY 10461
3Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany
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Francesca Voza,
Francesca Voza
2Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
3Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany
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Nader Ezzeddine,
Nader Ezzeddine
1Department of Medicine (Division of Cardiology), and Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, Bronx, NY 10461
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Manfred Frasch
Manfred Frasch
2Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
3Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany
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Hanh T. Nguyen
1Department of Medicine (Division of Cardiology), and Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, Bronx, NY 10461
3Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany
Francesca Voza
2Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
3Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany
Nader Ezzeddine
1Department of Medicine (Division of Cardiology), and Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, Bronx, NY 10461
Manfred Frasch
2Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
3Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany
Correspondence to M. Frasch: [email protected]; or H.T. Nguyen: [email protected]
N. Ezzeddine's present address is Department of Biochemistry and Molecular Biology, The University of Texas Houston Medical School, Houston, TX 77030.
Abbreviations used in this paper: mib2, Drosophila mind bomb2; mys, myospheroid; Neur, Neuralized.
Received:
August 20 2007
Accepted:
September 22 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 179 (2): 219–227.
Article history
Received:
August 20 2007
Accepted:
September 22 2007
Citation
Hanh T. Nguyen, Francesca Voza, Nader Ezzeddine, Manfred Frasch; Drosophila mind bomb2 is required for maintaining muscle integrity and survival . J Cell Biol 22 October 2007; 179 (2): 219–227. doi: https://doi.org/10.1083/jcb.200708135
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