A mutation in serca underlies motility dysfunction in accordion zebrafish

Area of Science:

• Developmental biology
• Neuroscience
• Muscle physiology

Background:

• Zebrafish develop fast swimming abilities early in development.
• The 'accordion' (acc) mutant exhibits abnormal, prolonged muscle contractions, hindering coordinated swimming.
• Neuromuscular transmission is not the primary cause of the acc motility defect.

Purpose of the Study:

• To investigate the molecular basis of the motility defect in the zebrafish 'accordion' (acc) mutant.
• To determine if the defect originates in the central nervous system or skeletal muscle.
• To identify the specific gene responsible for the acc phenotype.

Main Methods:

• Whole-cell recordings from zebrafish skeletal muscle.
• Imaging of calcium transients in larval acc zebrafish skeletal muscle.
• Positional cloning to identify the mutated gene.
• Antisense morpholino injection in wild-type zebrafish.

Main Results:

• Skeletal muscle of acc mutants shows prolonged calcium transients and contractions upon depolarization.
• Positional cloning identified a mutation in the SERCA gene as the cause of the acc phenotype.
• Antisense morpholino knockdown of SERCA in wild-type zebrafish recapitulated the acc phenotype, including impaired swimming.

Conclusions:

• The motility dysfunction in accordion zebrafish is caused by a mutation in SERCA, a sarcoplasmic reticulum calcium pump.
• Defective calcium transport in skeletal muscle, not central nervous system dysfunction, underlies the accordion phenotype.
• This study highlights the critical role of SERCA function in the development of coordinated swimming behaviors.