Horb M E, Thomsen G H
Department of Biochemistry and Cell Biology, Institute of Cell and Developmental Biology, State University of New York, Stony Brook, NY 11794-5215, USA.
Development. 1999 Apr;126(8):1739-51. doi: 10.1242/dev.126.8.1739.
Mutations in the Tbx5 transcription factor cause heart septal defects found in human Holt-Oram Syndrome. The complete extent to which Tbx5 functions in heart development, however, has not been established. Here we show that, in Xenopus embryos, Tbx5 is expressed in the early heart field, posterior to the cardiac homeobox transcription factor, Nkx2.5. During morphogenesis, Tbx5 is expressed throughout the heart tube except the anterior portion, the bulbus cordis. When Tbx5 activity is antagonized with a hormone-inducible, dominant negative version of the protein, the heart fails to develop. These results suggest that, in addition to its function in heart septation, Tbx5 has a more global role in cardiac specification and heart development in vertebrate embryos.
Tbx5转录因子的突变会导致人类霍尔特-奥拉姆综合征中出现的心脏间隔缺损。然而,Tbx5在心脏发育中的完整功能范围尚未确定。在此我们表明,在非洲爪蟾胚胎中,Tbx5在心脏早期区域表达,位于心脏同源框转录因子Nkx2.5的后方。在形态发生过程中,Tbx5在整个心脏管中表达,但不包括前部的动脉球。当用一种激素诱导的、该蛋白的显性负性版本拮抗Tbx5活性时,心脏无法发育。这些结果表明,除了其在心脏间隔形成中的功能外,Tbx5在脊椎动物胚胎的心脏特化和心脏发育中具有更广泛的作用。