δ- sarcoglycan is necessary for early heart and muscle development in zebrafish

Abstract

δ- sarcoglycan, one member of the sarcoglycan complex, is a very conservative muscle-specific protein exclusively expressed in the skeletal and cardiac muscles of vertebrates. Mutations in sarcoglycans are known to be involved in limb-girdle muscular dystrophy (LGMD) and dilated cardiomyopathy (DCM) in humans. To address the role of δ- sarcoglycan gene in zebrafish development, we have studied expression pattern of δ- sarcoglycan in zebrafish embryos and examined the role of δ- sarcoglycan in zebrafish embryonic development by morpholino. Strong expression of δ- sarcoglycan was observed in various muscles including those of the segment, heart, eye, jaw, pectoral fin, branchial arches, and swim bladder in zebrafish embryo. δ- sarcoglycan was also expressed in midbrain and retina. Knockdown of δ- sarcoglycan resulted in severe abnormality in both the cardiac and skeletal muscles. Some severe ones displayed serious morphological abnormality such as hypoplastic head, linear heart, very weak heartbeats, and runtish trunk, all dead within 5 dpf. Whole-mount in situ hybridization analysis showed that adaxial cells and muscle pioneers were affected in δ- sarcoglycan knockdown embryos. In addition, absence of δ- sarcoglycan protein severely delayed the cardiac development and influenced the differentiation of cardiac muscle, and the cardiac left-right asymmetry was dramatically changed in morpholino-treated embryos. These data together suggest that δ- sarcoglycan plays an important role in early heart and muscle development.