A DUPLICATED ZONE OF POLARIZING ACTIVITY IN POLYDACTYLOUS MOUSE MUTANTS
A DUPLICATED ZONE OF POLARIZING ACTIVITY IN POLYDACTYLOUS MOUSE MUTANTS
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DOI：
10.1101/gad.9.13.1645
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发表时间：
1995-07-01
影响因子：
10.5
通讯作者：
SHIROISHI, T
中科院分区：
文献类型：
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作者：
MASUYA, H;SAGAI, T;SHIROISHI, T
沿着发育中的脊椎动物肢体的前后轴的位置信号由位于后缘的极化活动区（ZPA）提供。最近，它被确定为音速刺猬（Shh）介导ZPA活动。在这里，我们报告了一个新的小鼠突变体，诱导突变体4（Rim 4），和两个旧的突变体，半额外的脚趾（Hx）和额外的脚趾（Xt），表现出镜像复制的骨骼模式的数字。这些突变体的胚胎原位杂交显示，在肢芽前缘的Shh和成纤维细胞生长因子-4（Fgf-4）基因的异位表达。新突变Rim 4定位于第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关联。在这个突变体中，异位表达的Hoxd-11基因，被认为是下游的ZPA，也观察到在前缘的肢芽。所有的结果表明，在这些突变体的肢芽前缘存在一个额外的ZPA。因此，似乎多个内源性基因调节ZPA在发育中的小鼠肢芽中的空间定位。
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.