The myotendinous junction (MTJ) is a specialized structure that transmits muscle contractile forces to tendon. Collagen XXII (COLXXII) is a novel component of MTJ (Koch et al., 2004). It belongs to the FACITs (Fibrils Associated Collagen with Interrupted Triple helix) subset of the collagen superfamily that is characterized by their capacity to mediate protein-protein interactions. The in vivo role of COLXXII has not been elucidated. Therefore, we decided to analyze its function in developing zebrafish using the morpholino-based knock-down strategy. We showed that its transcripts are exclusively expressed at the extremities of muscle fibers close to myoseptal tendons and the protein is deposited at the MTJ. The onset of COLXXII expression depends on FGF signaling, probably FGF8. Using different methods, we showed that loss of COLXXII induces morphofunctional alterations of muscle/tendon development and muscle weakness. Progressive muscle fiber detachment and retraction are observed in morphants that result from MTJ failure occuring at the muscle basement membrane/myosepta extracellular matrix side. The morphotype of the MO22-injected embryos is reminiscent to the sapje (dystrophin mutant) and candyfloss (laminin α2 chain mutation) mutant phenotypes indicating that COLXXII provides a molecular link between muscle and tendons. Our results suggest that COLXXII plays a crucial role in MTJ development and function and represents a novel candidate gene for muscular dystrophies.
