Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt/Fgf signaling cascade
Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt/Fgf signaling cascade
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DOI：
10.1242/dev.00474
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发表时间：
2003-06-01
期刊：
影响因子：
4.6
通讯作者：
Ogura, T
中科院分区：
文献类型：
--
作者：
Takeuchi, JK;Koshiba-Takeuchi, K;Ogura, T
成纤维细胞生长因子和Wnt家族成员之间的紧密环在脊椎动物肢体发育的启动中起关键作用。我们首次表明，Tbx 5和Tbx 4直接参与了这一过程。当这些Tbx基因的显性负性形式在鸡的预期肢体领域中被错误表达时，Wnt和Fgf基因的抑制引起无肢表型。相比之下，当Tbx 5和Tbx 4在侧翼中被错误表达时，分别诱导了额外的翼状和额外的腿状肢体。这些结果突出了Tbx 5和Tbx 4在肢体起始、前肢/后肢的特化和四足动物肢体的进化过程中的关键作用，将Tbx基因置于高度保守的遗传程序的中心。
A tight loop between members of the fibroblast growth factor and the Wnt families plays a key role in the initiation of vertebrate limb development. We show for the first time that Tbx5 and Tbx4 are directly involved in this process. When dominant-negative forms of these Tbx genes were misexpressed in the chick prospective limb fields, a limbless phenotype arose with repression of both Wnt and Fgf genes By contrast, when Tbx5 and Tbx4 were misexpressed in the flank, an additional wing-like and an additional leg-like limbs were induced, respectively. This additional limb formation was accompanied by the induction of both Wnt and Fgf genes These results highlight the pivotal roles of Tbx5 and Tbx4 during limb initiation, specification of forelimb/hindlimb and evolution of tetrapod limbs, placing Tbx genes at the center of a highly conserved genetic program.