Retinol dehydrogenase, RDHll, is essential for the heart development and cardiac performance in zebrafish

Background Retinoic acid （RA） is a potent signaling molecule that plays pleiotropic roles in patterning, morphogenesis, and organogenesis during embryonic development. The synthesis from retinol （vitamin A） to retinoic acid requires two sequential oxidative steps. The first step involves the oxidation of retinol to retinal through the action of retinol dehydrogenases. Retinol dehydrogenasesll （RDHll） is a novel zebrafish retinol dehydrogenase. Herein we investigated the role of zebrafish RDHll in heart development and cardiac performance in detail. Methods RDHll specific morpholino was used to reduce the function of RDHll in zebrafish. The gene expressions were observed by using whole mount in situ hybridization. Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization （hpf）. The cardiac performance was analyzed by measuring ventricular shortening fraction （VSF）. Results The knock-down of RDHll led to abnormal neural crest cells migration and reduced numbers of neural crest cells in RDHll morphant embryos. The reduced numbers of cardiac neural crest cells also can be seen in RDHll morphant embryos. Furthermore, the morpholino-mediated knock-down of RDHll resulted in the abnormal heart loop. The left-right determining genes expression pattern was altered in RDHll morphant embryos. The impaired cardiac performance was observed in RDHll morphant embryos. Taken together, these data demonstrate that RDHll is essential for the heart development and cardiac performance in zebrafish. Conclusions RDHll plays a important role in the neural crest cells development, and then ultimately affects the heart loop and cardiac performance. These results show for the first time that an enzyme involved in the retinol to retinaldehyde conversion participate in the heart development and cardiac performance in zebrafish.