Tbx genes specify posterior digit identity through Shh and BMP signaling

Tbx genes specify posterior digit identity through Shh and BMP signaling
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DOI:
10.1016/s1534-5807(03)00401-5
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发表时间:
2004-01-01
期刊:
影响因子:
11.8
通讯作者:
Ogura, T
Ogura, T
中科院分区:
生物学1区
文献类型:
--
作者:
Suzuki, T;Takeuchi, J;Ogura, T

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尽管对肢芽的前后轴(AP轴)的形成进行了广泛的研究,但沿着AP轴指定数字身份的机制仍然不清楚。以四位鸡腿为模型,我们在此报告,Tbx2和Tbx3分别指定数字IV和III的数字标识。Tbx2和Tbx3的错误表达分别导致了手指III到手指IV和手指II到手指III的后部同源转换。相反,它们的突变体VP16DeltaTbx2和VP16DeltaTbx3的错误表达诱导了前转化。在这两种情况下,都观察到了几个标志物(例如,BMP2、Shh和HoxD基因)的表达变化。此外,Tbx2和Tbx3挽救了Noggin介导的对叉指BMP信号的抑制,这是建立数字身份的关键信号。因此,我们得出结论,Tbx3指定数字III,而Tbx2和Tbx3的组合指定数字IV,与叉指BMP信令级联一起作用。
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 VP16DeltaTbx2 and VP16DeltaTbx3 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.