Masuya H, Sagai T, Wakana S, Moriwaki K, Shiroishi T
Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Japan.
Genes Dev. 1995 Jul 1;9(13):1645-53. doi: 10.1101/gad.9.13.1645.
The positional signaling along the anteroposterior axis of the developing vertebrate limb is provided by the zone of polarizing activity (ZPA) located at the posterior margin. Recently, it was established that the Sonic hedgehog (Shh) mediates ZPA activity. Here we report that a new mouse mutant, Recombination induced mutant 4 (Rim4), and two old mutants, Hemimelic extra toes (Hx) and Extra toes (Xt), exhibit mirror-image duplications of the skeletal pattern of the digits. In situ hybridization of the embryos of these mutants revealed ectopic expression of Shh and fibroblast growth factor-4 (Fgf-4) genes at the anterior margin of limb buds. The new mutation, Rim4, was mapped to chromosome 6 with linkage to HoxAbut segregated from HoxA. No linkage to other known polydactylous mutations was detected. In this mutant, ectopic expression of the Hoxd-11 gene, thought to be downstream of ZPA, was also observed at the anterior margin of the limb buds. All results indicate the presence of an additional ZPA at the anterior margin of limb buds in these mutants. Thus, it appears that multiple endogenous genes regulate the spatial localization of the ZPA in the developing mouse limb bud.
发育中脊椎动物肢体前后轴上的位置信号由位于后缘的极化活性区（ZPA）提供。最近，已确定音猬因子（Shh）介导ZPA活性。在此我们报告，一个新的小鼠突变体，重组诱导突变体4（Rim4），以及两个旧的突变体，半肢多指（Hx）和多指（Xt），表现出指骨骨骼模式的镜像重复。对这些突变体胚胎的原位杂交显示，肢体芽前边缘处Shh和成纤维细胞生长因子4（Fgf-4）基因的异位表达。新突变体Rim4被定位到6号染色体，与HoxA连锁但与HoxA分离。未检测到与其他已知多指突变的连锁关系。在这个突变体中，被认为位于ZPA下游的Hoxd-11基因在肢体芽前边缘也观察到异位表达。所有结果表明这些突变体的肢体芽前边缘存在额外的ZPA。因此，似乎多个内源基因调节发育中小鼠肢体芽中ZPA的空间定位。
