Fast-twitch myofibrils grow in proportion to Mylpf dosage in the zebrafish embryo

Abstract

Muscle cells become stronger by expanding myofibrils, the chains of sarcomeres that produce contraction. Here we investigate how Mylpf (Myosin Light Chain Phosphorylatable Fast) abundance impacts myofibril assembly in fast-twitch muscle. The two zebrafish Mylpf genes (mylpfaandmylpfb) are exclusively expressed in fast-twitch muscle. We show that these cells initially produce six times moremylpfamRNA and protein thanmylpfb. The combined Mylpf protein dosage is necessary for and proportionate to fast-twitch myofibril growth in the embryo. Fast-twitch myofibrils are severely reduced in themylpfa-/-mutant, leading to loss of high-speed movement; however, by persistent slow movement this mutant swims as far through time as its wild-type sibling. Although themylpfb-/-mutant has normal myofibrils, myofibril formation fails entirely in themylpfa-/-;mylpfb-/-double mutant, indicating that the two genes are collectively essential to myofibril formation. Fast-twitch myofibril width is restored in themylpfa-/-mutant by transgenic expression ofmylpfa-GFP,mylpfb-GFP, and by humanMYLPF-GFPto a degree corresponding linearly with GFP brightness. This correlate is inverted by expression ofMYLPFalleles that cause Distal Arthrogryposis, which reduce myofibril size in proportion to protein abundance. These effects indicate that Mylpf dosage controls myofibril growth, impacting embryonic development and lifelong health.