Background Tbxl is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbxl-/- animal models are derived from the neural crest cells during ...Background Tbxl is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbxl-/- animal models are derived from the neural crest cells during development. Although the morphological phenotypes of some Tbxl knock-down animal models have been well described, analysis of the cardiac performance is limited. Therefore, myocardial performance was explored in Tbxl morpholino injected zebrafish embryos. Methods To elucidate these issues, Tbxl specific morpholino was used to reduce the function of Tbxl in zebrafish. The differentiation of the myocardial cells was observed 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 and atrial shortening fraction.Results Tbxl morpholino injected embryos were characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. In addition, Tbxl knock down reduced the amount of pharyngeal neural crest cells in zebrafish. Abnormal cardiac morphology was visible in nearly 20% of the Tbxl morpholino injected embryos. The hearts in these embryos did not loop or loop incompletely. Importantly, cardiac performance and heart rate were reduced in Tbxl morpholino injected embryos.Conclusions Tbxl might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Cardiac performance is impaired by Tbxl knock down in zebrafish.展开更多
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 ret...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.展开更多
Advances in medical devices have revolutionized the treatment of human diseases,such as stents in occluded coronary artery,left ventricular assist devices in heart failure,pacemakers in arrhythmias,etc.Despite their s...Advances in medical devices have revolutionized the treatment of human diseases,such as stents in occluded coronary artery,left ventricular assist devices in heart failure,pacemakers in arrhythmias,etc.Despite their significance,the development of devices for reducing and avoiding the thrombosis formation,obtaining excellent mechanical performance,and achieving stable electronic physiology remains challenging and unresolved.Fortunately,nature serves as a good resource of inspirations,and brings us endless bioinspired physicochemical ideas to better the development of novel artificial materials and devices that enable us to potentially overcome the unresolved obstacles.Bioinspired approaches,in particularly,owe much of their current development in biology,chemistry,materials science,medicine and engineering to the design and fabrication of advanced devices.The application of bioinspired devices is a burgeoning area in these fields of research.In this perspective,we would take the cardiovascular device as one example to show how these bioinspired approaches could be used to build novel,advanced biomedical devices with precisely controlled functions.Here,bioinspired approaches are utilized to solve issues like thrombogenic,mechanical and electronic physiology problems in medical devices.Moreover,there is an outlook for future challenges in the development of bioinspired medical devices.展开更多
基金This work was supported by grants from the National Natural Science Foundation (No. 30772352), Doctoral Fund of Ministry of Education of China (new teacher) (No. 200802461110) and Research Scholar Fund from Fudan University, China.
文摘Background Tbxl is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbxl-/- animal models are derived from the neural crest cells during development. Although the morphological phenotypes of some Tbxl knock-down animal models have been well described, analysis of the cardiac performance is limited. Therefore, myocardial performance was explored in Tbxl morpholino injected zebrafish embryos. Methods To elucidate these issues, Tbxl specific morpholino was used to reduce the function of Tbxl in zebrafish. The differentiation of the myocardial cells was observed 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 and atrial shortening fraction.Results Tbxl morpholino injected embryos were characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. In addition, Tbxl knock down reduced the amount of pharyngeal neural crest cells in zebrafish. Abnormal cardiac morphology was visible in nearly 20% of the Tbxl morpholino injected embryos. The hearts in these embryos did not loop or loop incompletely. Importantly, cardiac performance and heart rate were reduced in Tbxl morpholino injected embryos.Conclusions Tbxl might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Cardiac performance is impaired by Tbxl knock down in zebrafish.
基金This work was supported by the grants from the National Natural Science Foundation of China (No. 30972959) and Doctoral Fund of Ministry of Education of China (new teacher) (No. 200802461110).
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.21673197,31570947)Young Overseas High-level Talents Introduction Plan,the 111 Project(No.B16029)the Fundamental Research Funds for the Central Universities of China(No.20720170050)
文摘Advances in medical devices have revolutionized the treatment of human diseases,such as stents in occluded coronary artery,left ventricular assist devices in heart failure,pacemakers in arrhythmias,etc.Despite their significance,the development of devices for reducing and avoiding the thrombosis formation,obtaining excellent mechanical performance,and achieving stable electronic physiology remains challenging and unresolved.Fortunately,nature serves as a good resource of inspirations,and brings us endless bioinspired physicochemical ideas to better the development of novel artificial materials and devices that enable us to potentially overcome the unresolved obstacles.Bioinspired approaches,in particularly,owe much of their current development in biology,chemistry,materials science,medicine and engineering to the design and fabrication of advanced devices.The application of bioinspired devices is a burgeoning area in these fields of research.In this perspective,we would take the cardiovascular device as one example to show how these bioinspired approaches could be used to build novel,advanced biomedical devices with precisely controlled functions.Here,bioinspired approaches are utilized to solve issues like thrombogenic,mechanical and electronic physiology problems in medical devices.Moreover,there is an outlook for future challenges in the development of bioinspired medical devices.