Abstract
Adenosine deaminases acting on RNA (ADARs) convert specific adenosines to inosines on dsRNA, which increase complexities of a gene product. ADAR3 is the third member of ADAR gene family; however the RNA editing activity of ADAR3 has not been demonstrated. To elucidate the biological functions of the ADAR3 during zebrafish development, the expression of adar3 was perturbed by the morpholino antisense oligonucleotide. The adar3 knock-down fish (morphant) developed abnormally. The abnormal phenotypes include small bodies, bulging midbrain, enlarged forth brain ventrical, touch insensitive, and death before 7 dpf (days post fertilization). I In situ hybridization showed that the expression of several neuronal markers differed in the brain regions between morphant and wildtype embryos. An elevated level of acridine orange positive granules was observed in the head and trunk of 24 hpf adar3 morphants, and an increase of apoptosis restricted to the head region at 36 hpf. The result of quantitative RT-PCR analyses revealed that the expression of neuroD in the 24 hpf and 36 hpf morphants was significantly reduced. In addition, expressions of many neuron-specific genes were significantly reduced in the 36 hpf morphant. The expressions of p53 and mdm2 mRNA increased dramatically in the 24 hpf and 36 hpf morphants. In situ hybridization of cxcr4b revealed that the migration of PLL (posterior lateral line) primordium was not effected in the morphants, but the results of activity stain suggested that the development of neuromasts was abnormal. These data suggested that ADAR3 participated in the early brain development of zebrafish.