Journal article
A critical role for the nuclear protein Akirin2 in the formation of mammalian muscle in vivo
Genesis (New York, N.Y. : 2000), Vol.57(5), e23286
05/2019
DOI: 10.1002/dvg.23286
PMID: 30801883
Abstract
Evolutionarily conserved Akirin nuclear proteins interact with chromatin remodeling complexes at gene enhancers and promoters, and have been reported to regulate cell proliferation and differentiation. Of the two mouse Akirin genes, Akirin2 is essential during embryonic development, with known in vivo roles in immune system function and the formation of the cerebral cortex. Here we demonstrate that Akirin2 is critical for mouse myogenesis, a tightly regulated developmental process through which myoblast precursors fuse to form mature skeletal muscle fibers. Loss of Akirin2 in somitic muscle precursor cells via Sim1‐Cre‐mediated excision of a conditional Akirin2 allele results in neonatal lethality. Mutant embryos exhibit a complete lack of forelimb, intercostal, and diaphragm muscles due to extensive apoptosis and loss of Pax3‐positive myoblasts. Severe skeletal defects, including craniofacial abnormalities, disrupted ossification, and rib fusions are also observed, attributable to lack of skeletal muscles as well as patchy Sim1‐Cre activity in the embryonic sclerotome. We further show that Akirin2 levels are tightly regulated during muscle cell differentiation in vitro, and that Akirin2 is required for the proper expression of muscle differentiation factors myogenin and myosin heavy chain. Our results implicate Akirin2 as a major regulator of mammalian muscle formation in vivo.
Details
- Title: Subtitle
- A critical role for the nuclear protein Akirin2 in the formation of mammalian muscle in vivo
- Creators
- Peter J Bosch - Department of Biology and Iowa Neuroscience InstituteUniversity of Iowa Iowa City IowaLeah C Fuller - Department of Biology and Iowa Neuroscience InstituteUniversity of Iowa Iowa City IowaJoshua A Weiner - Department of Biology and Iowa Neuroscience InstituteUniversity of Iowa Iowa City Iowa
- Resource Type
- Journal article
- Publication Details
- Genesis (New York, N.Y. : 2000), Vol.57(5), e23286
- DOI
- 10.1002/dvg.23286
- PMID
- 30801883
- ISSN
- 1526-954X
- eISSN
- 1526-968X
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa, award: Major project grant
- Language
- English
- Date published
- 05/2019
- Academic Unit
- Neurology; Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983997988402771
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