Dheen T, Sleptsova-Friedrich I, Xu Y, Clark M, Lehrach H, Gong Z, Korzh V
Institute of Molecular Agrobiology and Department of Biological Sciences, National University of Singapore, Singapore.
Development. 1999 Jun;126(12):2703-13. doi: 10.1242/dev.126.12.2703.
Several genes containing the conserved T-box region in invertebrates and vertebrates have been reported recently. Here, we describe three novel members of the T-box gene family in zebrafish. One of these genes, tbx-c, is studied in detail. It is expressed in the axial mesoderm, notably, in the notochordal precursor cells immediately before formation of the notochord and in the chordoneural hinge of the tail bud, after the notochord is formed. In addition, its expression is detected in the ventral forebrain, sensory neurons, fin buds and excretory system. The expression pattern of tbx-c differs from that of the other two related genes, tbx-a and tbx-b. The developmental role of tbx-c has been analysed by overexpression of the full-length tbx-c mRNA and a truncated form of tbx-c mRNA, which encodes the dominant-negative Tbx-c. Overexpression of tbx-c causes expansion of the midline mesoderm and formation of ectopic midline structures at the expense of lateral mesodermal cells. In dominant-negative experiments, the midline mesoderm is reduced with the expansion of lateral mesoderm to the midline. These results suggest that tbx-c plays a role in formation of the midline mesoderm, particularly, the notochord. Moreover, modulation of tbx-c activity alters the development of primary motor neurons. Results of in vitro analysis in zebrafish animal caps suggest that tbx-c acts downstream of early mesodermal inducers (activin and ntl) and reveal an autoregulatory feedback loop between ntl and tbx-c. These data and analysis of midline (ntl-/- and flh-/-) and lateral mesoderm (spt-/-) mutants suggest that tbx-c may function during formation of the notochord.
最近有报道称，在无脊椎动物和脊椎动物中发现了几个含有保守T盒区域的基因。在此，我们描述了斑马鱼T盒基因家族的三个新成员。其中一个基因tbx - c得到了详细研究。它在轴中胚层表达，特别是在脊索形成前的脊索前体细胞中，以及在脊索形成后的尾芽的脊神经铰链中表达。此外，在腹侧前脑、感觉神经元、鳍芽和排泄系统中也检测到了它的表达。tbx - c的表达模式与另外两个相关基因tbx - a和tbx - b不同。通过全长tbx - c mRNA和编码显性负性Tbx - c的截短形式的tbx - c mRNA的过表达，分析了tbx - c的发育作用。tbx - c的过表达导致中线中胚层扩张，并以牺牲外侧中胚层细胞为代价形成异位中线结构。在显性负性实验中，中线中胚层减少，外侧中胚层向中线扩张。这些结果表明，tbx - c在中线中胚层，特别是脊索的形成中发挥作用。此外，tbx - c活性的调节会改变初级运动神经元的发育。斑马鱼动物帽的体外分析结果表明，tbx - c在早期中胚层诱导因子（激活素和ntl）的下游起作用，并揭示了ntl和tbx - c之间的自调节反馈环。这些数据以及对中线（ntl - / - 和flh - / - ）和外侧中胚层（spt - / - ）突变体的分析表明，tbx - c可能在脊索形成过程中发挥作用。
