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Published online October 22, 2007
doi:10.1083/jcb.200708135
The Journal of Cell Biology, Vol. 179, No. 2, 219-227
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Nguyen et al.
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 Drosophila mind bomb2 is required for maintaining muscle integrity and survival

Hanh T. Nguyen1,3, Francesca Voza2,3, Nader Ezzeddine1, and Manfred Frasch2,3

1 Department of Medicine (Division of Cardiology), and Department of Molecular and Developmental Biology, Albert Einstein College of Medicine, Bronx, NY 10461
2 Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
3 Department of Developmental Biology, The University of Erlangen-Nürnberg, Erlangen 91058, Germany

Correspondence to M. Frasch: manfred.frasch{at}biologie.uni-erlangen.de; or H.T. Nguyen: hnguyen{at}biologie.uni-erlangen.de

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.

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.


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