Journal
DEVELOPMENTAL BIOLOGY
Volume 311, Issue 2, Pages 359-368Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2007.08.032
Keywords
Dicer; miRNA; myogenesis; morphogenesis; apoptosis
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Funding
- NIAMS NIH HHS [F32 AR052581-02, F32 AR052581, AR46799, R01 AR046799-07, AR052581, R01 AR046799-08, R01 AR046799] Funding Source: Medline
- NIA NIH HHS [R01 AG020911, AG20911, R01 AG020911-05] Funding Source: Medline
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microRNAs (miRNAs) regulate gene expression post-transcriptionally by targeting mRNAs for degradation or by inhibiting translation. Dicer is an RNase III endonuclease which processes miRNA precursors into functional 21-23 nucleotide RNAs that are subsequently incorporated into the RNA-induced silencing complex. miRNA-mediated gene regulation is important for organogenesis of a variety of tissues including limb, lung and skin. To gain insight into the roles of Dicer and miRNAs in mammalian skeletal muscle development, we eliminated Dicer activity specifically in the myogenic compartment during embryogenesis. Dicer activity is essential for normal muscle development during embryogenesis and Dicer muscle mutants have reduced muscle miRNAs, die perinatally and display decreased skeletal muscle mass accompanied by abnormal myofiber morphology. Dicer mutant muscles also show increased apoptosis and Cre-mediated loss of Dicer in Myod-converted myoblasts results in enhanced cell death. These observations demonstrate key roles for Dicer in skeletal muscle and implicate miRNAs as critical components required for embryonic myogenesis. (c) 2007 Elsevier Inc. All rights reserved.
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