Takada S, Stark K L, Shea M J, Vassileva G, McMahon J A, McMahon A P
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
Genes Dev. 1994 Jan;8(2):174-89. doi: 10.1101/gad.8.2.174.
Amphibian studies have implicated Wnt signaling in the regulation of mesoderm formation, although direct evidence is lacking. We have characterized the expression of 12 mammalian Wnt-genes, identifying three that are expressed during gastrulation. Only one of these, Wnt-3a, is expressed extensively in cells fated to give rise to embryonic mesoderm, at egg cylinder stages. A likely null allele of Wnt-3a was generated by gene targeting. All Wnt-3a-/Wnt-3a- embryos lack caudal somites, have a disrupted notochord, and fail to form a tailbud. Thus, Wnt-3a may regulate dorsal (somitic) mesoderm fate and is required, by late primitive steak stages, for generation of all new embryonic mesoderm. Wnt-3a is also expressed in the dorsal CNS. Mutant embryos show CNS dysmorphology and ectopic expression of a dorsal CNS marker. We suggest that dysmorphology is secondary to the mesodermal and axial defects and that dorsal patterning of the CNS may be regulated by inductive signals arising from surface ectoderm.
两栖动物研究表明Wnt信号传导参与中胚层形成的调控，尽管缺乏直接证据。我们已对12种哺乳动物Wnt基因的表达进行了特征分析，确定了3种在原肠胚形成期间表达的基因。其中只有一种，即Wnt-3a，在卵柱期大量表达于注定会产生胚胎中胚层的细胞中。通过基因打靶产生了一个可能的Wnt-3a无效等位基因。所有Wnt-3a-/Wnt-3a-胚胎均缺乏尾节，脊索中断，且无法形成尾芽。因此，Wnt-3a可能调控背侧（体节）中胚层命运，并且在原始条带后期阶段是生成所有新的胚胎中胚层所必需的。Wnt-3a也在背侧中枢神经系统中表达。突变胚胎显示中枢神经系统形态异常以及背侧中枢神经系统标志物的异位表达。我们认为形态异常是中胚层和轴缺陷的继发结果，并且中枢神经系统的背侧模式可能受来自表面外胚层的诱导信号调控。
