Tbx1 Knock-down leads to reduced pharyngeal neural crest cells and cardiac performance in zebrafish

  • Miss Lifeng Zhang, Cardiovascular center, Children’s Hospital of Fudan University, China
  • Dr Yuexiang Wang, Shanghai Medical School & Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China
  • Dr Qiu Jiang, Shanghai Medical School & Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China
  • Miss Houyan Song, Shanghai Medical School & Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China
  • Dr Yonghao Gui, Cardiovascular center, Children’s Hospital of Fudan University, China

    • Objective: Tbx1 is the most promising candidate gene for DiGeorge syndrome. The phenotypes of Tbx1 knock-down in some animal models have been well described morphologically; however, the cardiac performance analysis of Tbx1 knock-down is limited. We aim to explore the roles of Tbx1 in cardiac neural crest and myocardial development in zebrafish.
    Methods: To elucidate these issues, Tbx1 specific morpholino was used to reduce the amount of Tbx1 in zebrafish. We studied cardiac differentiation in Tbx1 morphant embryos using whole mount in situ hybridization. Heart rates were counted in Tbx1 morphant embryos. The cardiac performance was analyzed by measuring VSF, ASF in Tbx1 morphant embryos.
    Results: Tbx1 morphant embryos are characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. The expression of crestin, hand2 and dlx2α in neural crest cells are extremely reduced, especially in the posterior arches.Tbx1 knock down may reduce the amount of pharyngeal neural crest cells in zebrafish. At the meantime, heart rate was decreased in Tbx1 morphant embryo when compared to that in control embryo. Decreased cardiac performance was observed in Tbx1 morphant embryos, VSF and ASF are both repressed due to Tbx1 knock-down when compared to that in control embryos.
    Conclusions: Our results suggest that Tbx1 might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Tbx1 Knock-down causes impaired cardiac performance in Tbx1 morphant embryos. These results will shed new insight into the roles of Tbx1 in the etiology of DGS