Takeuchi Jun K, Koshiba-Takeuchi Kazuko, Suzuki Takayuki, Kamimura Mika, Ogura Keiko, Ogura Toshihiko
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0101, Japan.
Development. 2003 Jun;130(12):2729-39. doi: 10.1242/dev.00474.
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.
成纤维细胞生长因子家族成员与Wnt家族成员之间的紧密循环在脊椎动物肢体发育的起始过程中起关键作用。我们首次表明，Tbx5和Tbx4直接参与这一过程。当这些Tbx基因的显性负性形式在鸡的预期肢体区域中错误表达时，会出现无肢表型，同时Wnt和Fgf基因均受到抑制。相比之下，当Tbx5和Tbx4在侧翼错误表达时，分别诱导出额外的翅膀样和腿样肢体。这种额外肢体的形成伴随着Wnt和Fgf基因的诱导。这些结果突出了Tbx5和Tbx4在肢体起始、前肢/后肢特化以及四足动物肢体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。
