Holland N D, Zhang S C, Clark M, Panopoulou G, Lehrach H, Holland L Z
Marine Biology Research Division, Scripps Institution of Oceanography, La Jolla, California 92093-0202, USA.
Dev Dyn. 1997 Sep;210(1):11-8. doi: 10.1002/(SICI)1097-0177(199709)210:1<11::AID-AJA2>3.0.CO;2-4.
Tob is a member of the PC3/ BTG1/Tob family of vertebrate tumor suppressor genes; its expression is known to inhibit proliferation of cells in vitro, but its possible roles during normal development have not been investigated previously. The present study concerns the structure and developmental expression of AmphiTob in an invertebrate chordate, amphioxus. This is the first investigation of any Tob gene during embryological development. The 311 amino acid AmphiTob protein is similar to vertebrate Tob but lacks the C-terminal PQ-rich domain of the latter. In early embryos of amphioxus, in situ hybridization first reveals AmphiTob expression in the hypoblast at the gastrula stage on the likely dorsal side of the embryo. During subsequent development, expression is seen in several tissues of the ectoderm, mesoderm, and endoderm. The most striking expression domains are in the developing somitic musculature and dorsal nerve cord. In the medial wall of each somite, AmphiTob is expressed strongly by cells destined to differentiate into the axial trunk muscles; this pattern persists until late in the larval stage, evidently because undifferentiated cells are continually becoming myogenic as the muscles grow. Nerve cord cells conspicuously transcribe AmphiTob from the late neurula until the early larval stage: Expression occurs in a few cells scattered along the nerve cord and in a group of cells located in the cerebral vesicle (in a region presumably homologous to the vertebrate diencephalic forebrain). During development, an intense and transitory transcription of AmphiTob may be an early event in cells exiting the cell cycle in preparation for differentiation.
Tob是脊椎动物肿瘤抑制基因PC3/BTG1/Tob家族的成员;已知其表达可在体外抑制细胞增殖,但此前尚未研究其在正常发育过程中的可能作用。本研究关注无脊椎脊索动物文昌鱼中AmphiTob的结构和发育表达情况。这是首次在胚胎发育过程中对任何Tob基因进行的研究。311个氨基酸的AmphiTob蛋白与脊椎动物的Tob相似,但缺少后者的C端富含PQ的结构域。在文昌鱼的早期胚胎中,原位杂交首先显示在原肠胚阶段胚胎可能的背侧下胚层中有AmphiTob表达。在随后的发育过程中,在外胚层、中胚层和内胚层的多个组织中都能看到表达。最显著的表达区域是在发育中的体节肌肉组织和背神经索中。在每个体节的内侧壁,AmphiTob由注定分化为轴向躯干肌肉的细胞强烈表达;这种模式一直持续到幼虫晚期,显然是因为随着肌肉生长,未分化细胞不断分化为肌细胞。从神经胚晚期到幼虫早期,神经索细胞显著转录AmphiTob:表达发生在沿神经索分散的少数细胞以及位于脑泡中的一组细胞中(在一个大概与脊椎动物间脑前脑同源的区域)。在发育过程中,AmphiTob强烈且短暂的转录可能是细胞退出细胞周期以准备分化的早期事件。