Vogel A, Rodriguez C, Warnken W, Izpisúa Belmonte J C
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature. 1995 Dec 14;378(6558):716-20. doi: 10.1038/378716a0.
The positional cues that govern the fate of cells along the dorsoventral axis of the developing vertebrate limb are established in the mesoderm before outgrowth of limb buds. In Drosophila, a LIM/-homeodomain gene, apterous, expressed in the dorsal compartment of the wing disc, specifies dorsal cell fate. Here we report the isolation of a vertebrate LIM-homeodomain containing gene, Chick Lmx1 (C-Lmx1). Transcripts for C-Lmx1 are detected in the presumptive dorsal limb mesoderm and are restricted thereafter to the dorsal mesoderm of the developing chick bud. C-Lmx1 expression is regulated by the overlying ectoderm where Wnt7a messenger RNA is localized. Wnt7a, required for normal development of the dorsoventral axis in mouse limbs, can induce ectopic expression of C-Lmx1 in ventral mesoderm. Misexpression of C-Lmx1 during limb outgrowth causes ventral to dorsal transformations of limb mesoderm. We propose that C-Lmx1 specifies dorsal cell fate during chick limb development.
在脊椎动物肢体发育过程中，决定沿背腹轴细胞命运的位置线索在肢芽长出之前就在中胚层中建立起来了。在果蝇中，一个在翅盘背侧区表达的含LIM/同源异型结构域基因apterous，决定了背侧细胞的命运。在此我们报告一个含有脊椎动物LIM-同源异型结构域基因——鸡Lmx1（C-Lmx1）的分离。在假定的背侧肢体中胚层中检测到C-Lmx1的转录本，随后局限于发育中的鸡芽的背侧中胚层。C-Lmx1的表达受上方外胚层调控，Wnt7a信使核糖核酸定位于此。Wnt7a是小鼠肢体背腹轴正常发育所必需的，它能诱导C-Lmx1在腹侧中胚层异位表达。在肢体生长过程中C-Lmx1的错误表达会导致肢体中胚层从腹侧到背侧的转变。我们认为C-Lmx1在鸡肢体发育过程中决定背侧细胞的命运。
