Strähle U, Jesuthasan S, Blader P, Garcia-Villalba P, Hatta K, Ingham P W
IGBMC, CNRS/INSERM/ULP, Illkirch, France.
Genes Funct. 1997 Apr;1(2):131-48. doi: 10.1046/j.1365-4624.1997.00010.x.
Axial midline structures play a central role as signalling centres during the development of the vertebrate embryo. We have isolated mutant alleles of a new locus, one-eyed pinhead (oep), in the zebrafish that are characterized by cyclopia and impaired development of the floor plate. oep mutants fail to establish expression of axial (zebrafish HNF3beta) and sonic hedgehog in the midline of the neural plate but form a notochord that expresses both genes. In the spinal cord of the 1-day-old embryo, mutation of oep impairs floor-plate but not motor-neuron development. Floor-plate development is absolutely dependent on oep only at early stages, since partial recovery of the floor plate can be detected at 48 h in the spinal cord, suggesting compensatory pathways. Ectopic expression of sonic hedgehog and a dominant-negative protein kinase A regulatory subunit induces expression of floor-plate marker genes in the oep mutant neural tube in a manner indistinguishable from wild-type embryos. Our data suggest that the oep mutation does not impair Sonic hedgehog signalling and thus implicate a second process that acts synergistically with Sonic hedgehog signalling in the specification of the midline of the neuroectoderm and that can partially be compensated for during later development.
在脊椎动物胚胎发育过程中，轴中线结构作为信号中心发挥着核心作用。我们在斑马鱼中分离出了一个新基因座——独眼针头（oep）的突变等位基因，其特征为独眼畸形和底板发育受损。oep突变体无法在神经板中线建立轴向（斑马鱼HNF3β）和音猬因子的表达，但能形成表达这两种基因的脊索。在1日龄胚胎的脊髓中，oep突变会损害底板发育，但不会影响运动神经元发育。底板发育仅在早期绝对依赖oep，因为在脊髓中48小时时可检测到底板有部分恢复，提示存在补偿途径。音猬因子和一种显性负性蛋白激酶A调节亚基的异位表达，以与野生型胚胎无法区分的方式在oep突变体神经管中诱导底板标记基因的表达。我们的数据表明，oep突变不会损害音猬因子信号传导，因此暗示了另一个与音猬因子信号传导协同作用于神经外胚层中线特化的过程，并且在后期发育中可以部分得到补偿。
