Department of Molecular Oncology ; Global COE Program.
Biol Open. 2012 May 15;1(5):458-66. doi: 10.1242/bio.2012638. Epub 2012 Mar 27.
The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
膜锚定金属蛋白酶调节剂 RECK 已被鉴定为肿瘤抑制因子。在这里，我们报告说，Reck 表达减少的小鼠表现出肢体异常，包括后轴骨骼元素中右优势的、前肢特异性缺陷。低 Reck 突变体的前肢芽具有改变的背侧外胚层，Wnt7a 和 Igf2 表达减少，两个信号中心（即 ZPA 和 AER）的萎缩，这对于肢体的生长和模式至关重要。Reck 在正常肢芽的前间充质中大量表达；间充质特异性 Reck 失活再现了低 Reck 表型；一些致畸剂下调间充质细胞中的 Reck。我们的研究结果说明了 Reck 在哺乳动物发育中对间充质-上皮相互作用所必需的作用。
