Abstract
Optimal cell performance depends on cell size and the appropriate relative size, i.e., scaling, of the nucleus. How nuclear scaling is regulated and contributes to cell function is poorly understood, especially in skeletal muscle fibers, which are among the largest cells, containing hundreds of nuclei. Here, we present a Drosophila in vivo system to analyze nuclear scaling in whole multinucleated muscle fibers, genetically manipulate individual components, and assess muscle function. Despite precise global coordination, we find that individual nuclei within a myofiber establish different local scaling relationships by adjusting their size and synthetic activity in correlation with positional or spatial cues. While myonuclei exhibit compensatory potential, even minor changes in global nuclear size scaling correlate with reduced muscle function. Our study provides the first comprehensive approach to unraveling the intrinsic regulation of size in multinucleated muscle fibers. These insights to muscle cell biology will accelerate the development of interventions for muscle diseases. Muscle fibers are large multinucleated cells with remarkable size plasticity. Windner et al. investigate the relationship between muscle cell size and nuclear content. They show that cells contain a heterogeneous population of nuclei and explore mechanisms of nuclear coordination, as well as the functional consequences of scaling perturbations.
Original language | English (US) |
---|---|
Pages (from-to) | 48-62.e3 |
Journal | Developmental Cell |
Volume | 49 |
Issue number | 1 |
DOIs | |
State | Published - Apr 8 2019 |
Keywords
- Drosophila
- Fibrillarin
- cell size
- nuclear positioning
- nuclear scaling
- nuclear synthetic activity
- nucleolus
- polyploidy
- skeletal muscle
- syncytial organization
ASJC Scopus subject areas
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- Developmental Biology
- Cell Biology