Suzuki Takayuki, Takeuchi Jun, Koshiba-Takeuchi Kazuko, Ogura Toshihiko
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0101, Japan.
Dev Cell. 2004 Jan;6(1):43-53. doi: 10.1016/s1534-5807(03)00401-5.
Despite extensive studies on the anterior-posterior (AP) axis formation of limb buds, mechanisms that specify digit identities along the AP axis remain obscure. Using the four-digit chick leg as a model, we report here that Tbx2 and Tbx3 specify the digit identities of digits IV and III, respectively. Misexpression of Tbx2 and Tbx3 induced posterior homeotic transformation of digit III to digit IV and digit II to digit III, respectively. Conversely, misexpression of their mutants VP16 Delta Tbx2 and VP16 Delta Tbx3 induced anterior transformation. In both cases, alterations in the expression of several markers (e.g., BMP2, Shh, and HoxD genes) were observed. In addition, Tbx2 and Tbx3 rescued Noggin-mediated inhibition of interdigital BMP signaling, signaling which is pivotal in establishing digit identities. Hence, we conclude that Tbx3 specifies digit III, and the combination of Tbx2 and Tbx3 specifies digit IV, acting together with the interdigital BMP signaling cascade.
尽管对肢体芽的前后（AP）轴形成进行了广泛研究，但沿AP轴确定指（趾）身份的机制仍不清楚。以具有四个趾的鸡腿部为模型，我们在此报告，Tbx2和Tbx3分别确定了趾IV和趾III的指（趾）身份。Tbx2和Tbx3的错误表达分别诱导了趾III向后同源转化为趾IV以及趾II向后同源转化为趾III。相反，其突变体VP16 ΔTbx2和VP16 ΔTbx3的错误表达诱导了向前转化。在这两种情况下，均观察到几种标志物（如BMP2、Shh和HoxD基因）表达的改变。此外，Tbx2和Tbx3挽救了Noggin介导的对趾间BMP信号传导的抑制作用，该信号传导在建立指（趾）身份中起关键作用。因此，我们得出结论，Tbx3确定趾III，Tbx2和Tbx3的组合确定趾IV，它们与趾间BMP信号级联共同起作用。
