Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos
Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos
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DOI：
10.1111/j.0021-8782.2004.00309.x
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发表时间：
2004-07-01
影响因子：
2.4
通讯作者：
Jung, HS
中科院分区：
文献类型：
--
作者：
Eblaghie, MC;Song, SJ;Jung, HS
Wnts、Fgfs和Tbx基因之间的相互作用参与肢体起始，并且相同的基因家族也与乳腺发育有关。在这里，我们探讨这些基因如何共同作用于乳腺启动。我们比较了与人类尺乳综合征相关的基因Tbx 3的表达，编码双特异性MAPK磷酸酶Pyst 1/MKP 3的基因的表达，这是对FGFR 1信号传导的早期反应。（通过对SU 5402抑制剂的敏感性判断），和Lef 1的表达，编码介导Wnt信号传导的转录因子和迄今已知在乳腺发育中表达的最早基因。我们发现Tbx 3的表达早于Lef 1，Pyst 1也表达早，但只是短暂的。Tbx 3、Pyst 1和Lef 1在不同腺体中的表达模式表明，乳腺起始的顺序为3、4、1、2和5。与Pyst 1在乳腺中的表达一致，我们在表面外胚层和乳腺芽上皮中检测到Fgfr 1b、Fgf 8和Fgf 9的表达，在乳腺芽上皮中检测到Fgf 4和Fgf 17的表达。将浸泡在FGF-8中的珠子应用于小鼠胚胎的侧腹，在乳腺芽开始之前的阶段，诱导Pyst 1和Lef 1的表达，并在珠子周围的侧腹组织中维持Tbx 3的表达。浸泡在FGFR 1抑制剂SU 5402中的移植珠消除了Tbx 3，Pyst 1和Lef 1表达，支持FGFR 1信号传导是早期乳腺启动所需的观点。我们还表明，阻断Wnt信号传导废除Tbx 3的表达，但不是Pyst 1的表达。这些数据，与以前的研究结果一起，提出了一种模型，其中Tbx 3的表达是诱导和维持在早期腺体启动的Wnt和Fgf信号通过FGFR 1。
Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and the same gene families have been implicated in mammary gland development. Here we explore how these genes act together in mammary gland initiation. We compared expression of Tbx3, the gene associated with the human condition ulnar-mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a transcription factor mediating Wnt signalling and the earliest gene so far known to be expressed in mammary gland development. We found that Tbx3 is expressed earlier than Lef1 and that Pyst1 is also expressed early but only transiently. Patterns of expression of Tbx3, Pyst1 and Lef1 in different glands suggest that the order of mammary gland initiation is 3, 4, 1, 2 and 5. Consistent with expression of Pyst1 in the mammary gland, we detected expression of Fgfr1b, Fgf8 and Fgf9 in both surface ectoderm and mammary bud epithelium, and Fgf4 and Fgf17 in mammary bud epithelium. Beads soaked in FGF-8 applied to the flank of mouse embryos, at a stage just prior to mammary bud initiation, induce expression of Pyst1 and Lef1 and maintain Tbx3 expression in flank tissue surrounding the bead. Grafting beads soaked in the FGFR1 inhibitor, SU5402, abolishes Tbx3, Pyst1 and Lef1 expression, supporting the idea that FGFR1 signalling is required for early mammary gland initiation. We also showed that blocking Wnt signalling abolishes Tbx3 expression but not Pyst1 expression. These data, taken together with previous findings, suggest a model in which Tbx3 expression is induced and maintained in early gland initiation by both Wnt and Fgf signalling through FGFR1.