Journal
DEVELOPMENT
Volume 143, Issue 16, Pages 2965-2972Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.139485
Keywords
Zebrafish; Muscle morphogenesis; Extracellular matrix; Cardiac fusion
Categories
Funding
- National Institutes of Health (NIH) [R01 HL069594, R01 HL133166]
- March of Dimes Foundation [1-FY08-589]
- Association Francaise contre les Myopathies [MNM1 2013-16528]
- American Heart Association
- Children's Heart Foundation [13POST16870010, 15POST25080308]
- UCSD Cell and Molecular Genetics Training Program [NIH] [T32 GM007240]
- American Heart Association [15PRE22480001]
Ask authors/readers for more resources
Skeletal muscle morphogenesis depends upon interactions between developing muscle fibers and the extracellular matrix (ECM) that anchors fibers to the myotendinous junction (MTJ). The pathways that organize the ECM and regulate its engagement by cell-matrix adhesion complexes (CMACs) are therefore essential for muscle integrity. Here, we demonstrate the impact of transmembrane protein 2 (tmem2) on cell-matrix interactions during muscle morphogenesis in zebrafish. Maternal-zygotic tmem2 mutants (MZtmem2) exhibit muscle fiber detachment, in association with impaired laminin organization and ineffective fibronectin degradation at the MTJ. Similarly, disorganized laminin and fibronectin surround MZtmem2 cardiomyocytes, which could account for their hindered movement during cardiac morphogenesis. In addition to ECM defects, MZtmem2 mutants display hypoglycosylation of alpha-dystroglycan within the CMAC, which could contribute to the observed fiber detachment. Expression of the Tmem2 ectodomain can rescue aspects of the MZtmem2 phenotype, consistent with a possible extracellular function of Tmem2. Together, our results suggest that Tmem2 regulates cell-matrix interactions by affecting both ECM organization and CMAC activity. These findings evoke possible connections between the functions of Tmem2 and the etiologies of congenital muscular dystrophies, particularly dystroglycanopathies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available