(The) role of Transmembrane 4 L6 family member 5 in the development of zebrafish

Abstract

Transmembrane 4 L6 family member 5 (TM4SF5), a member of tetraspanin L6 superfamily, is a glycoprotein which has four transmembrane domains. TM4SF5 has been reported to be closely involved in tumorigenesis, being a signaling regulator during communication between tumor cells and tumor microenvironment via interaction with various proteins such as growth factor receptors, integrin receptors. It has been shown that TM4SF5 regulates important cellular processes like epithelial-to-mesenchymal transition (EMT), which is importantly functional for development of live fibrosis, tumorigenesis, and cell migration/invasion. In zebrafish, somitogenesis and myotome formation are the processes that a wide range of cellular processes including cell migration/adhesion, EMT and morphological changes occur simultaneously. However, the function of TM4SF5 during embryogenesis in which EMT and cell migration/adhesion are crucial remains unknown. Here we investigated the function of TM4SF5 in zebrafish embryogenesis. Expression of tm4sf5 mRNA was elevated during somitogenesis, and deteced in porsterior somites. After 1 dpf, tm4sf5 transcripts were detected in whole myotome. Knock-down of tm4sf5 using morpholino oligonuceotides resulted in an aberrant development of trunk and abnormal morphology of muscle fibers. The overall muscle mass was also reduced in tm4sf5 morphants. In addition, the knock-down of tm4sf5 altered expression of integrin alpha5, which is known to be expressed in muscle pioneer and necessary for somite boundary maintenance. Because the somite boundaries mature into myotome boundaries and necessary for proper morphogenesis of muscle fibers, we could infer that tm4sf5-dependentt integrin alpha5 expression or function is important for normal myotome formation. Taken together, these observations suggest that TM4SF5 plays a regulatory role in zebrafish embryogenesis, especially in myogenic processes, presumably via collaborations with integrin alpha5.