ADP-ribosylation-like factor-6 interacting protein is required for neural crest development in zebrafish embryos


ADP-ribosylation-like factor-6 interacting protein (Arl6ip) is an interacting protein of Arl6 which is one of the small ADP ribosylation factor GTP-binding proteins that are major regulators in intracellular traffic. Although the in vitro function of arl6ip gene is suggested as protein transport, membrane trafficking, or cell signaling during hematopoietic maturation, the in vivo roles that alr6ip plays during embryonic development are totally unknown. Here, we demonstrated that whe Arl6ip was lost by injecting the zebrafish embryos an antisense morpholino oligonucleotides (MO) which inhibited arl6ip mRNA translation specifically, the neural crest derivatives, such as cartilage, cranial ganglia, peripheral neurons, and heart, were defective. The expressions of neural plate border specifiers, msxb, dlx3b, and tfap2a, were normal, but the expression of neural crest specification genes, foxd3, snail1b and sox10 were reduced, implicating arl6ip is essential for neural crest specification. In addition, apoptosis was apparent occurrence in the pre-migratory neural crest cells, indicating a critical role for arl6ip in the survival of neural crest cells. Furthermore, crestin and sox10, which were expressed in the cranial and trunk migrating neural crest cells, were also decreased, suggesting that arl6ip is not only required for neural crest migration. Interestingly, we noticed that the hearts of the arl6ip-MO-injected embryos were failure to undergo normal looping and the function of heart was depressed. This defective heart may result from the loss of cardiac pre-migratory neural crest cells. Taken together, we conclude that arl6ip is required for neural crest specification, survival, and migration. This is the first report that demonstrates the in vivo function of arl6ip during neural crest development.