Isaacs H V, Pownall M E, Slack J M
Developmental Biology Programme, School of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
EMBO J. 1998 Jun 15;17(12):3413-27. doi: 10.1093/emboj/17.12.3413.
The caudal gene codes for a homeodomain transcription factor that is required for normal posterior development in Drosophila. In this study the biological activities of the Xenopus caudal (Cdx) family member Xcad3 are examined. A series of domain-swapping experiments demonstrate that the N-terminus of Xcad3 is necessary for it to activate Hox gene expression and that this function can be replaced by the activation domain from the viral protein VP16. In addition, experiments using an Xcad3 repressor mutant (XcadEn-R), which potently blocks the activity of wild-type Xcad3, are reported. Overexpression of XcadEn-R in embryos inhibits the activation of the same subset of Hox genes that are activated by wild-type Xcad3 and leads to a dramatic disruption of posterior development. We show that Xcad3 is an immediate early target of the FGF signalling pathway and that Xcad3 posteriorizes anterior neural tissue in a similar way to FGF. Furthermore, Xcad3 is required for the activation of Hox genes by FGFs. These data provide strong evidence that Xcad3 is required for normal posterior development and that it regulates the expression of the Hox genes downstream of FGF signalling.
尾端基因编码一种同源结构域转录因子，它是果蝇正常后部发育所必需的。在本研究中，对非洲爪蟾尾端（Cdx）家族成员Xcad3的生物学活性进行了检测。一系列结构域交换实验表明，Xcad3的N端对于激活Hox基因表达是必需的，并且该功能可被病毒蛋白VP16的激活结构域所取代。此外，还报道了使用一种能有效阻断野生型Xcad3活性的Xcad3阻遏突变体（XcadEn-R）所做的实验。在胚胎中过表达XcadEn-R会抑制与野生型Xcad3激活的相同Hox基因子集的激活，并导致后部发育的显著破坏。我们表明，Xcad3是FGF信号通路的一个即时早期靶点，并且Xcad3以与FGF相似的方式使前侧神经组织向尾侧分化。此外，FGF激活Hox基因需要Xcad3。这些数据提供了强有力的证据，表明Xcad3是正常后部发育所必需的，并且它在FGF信号通路下游调节Hox基因的表达。
