Dishevelled limits Notch signalling through inhibition of CSL.
Dishevelled limits Notch signalling through inhibition of CSL.
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DOI：
10.1242/dev.081885
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Brennan K
中科院分区：
文献类型：
--
作者：
Collu GM;Hidalgo-Sastre A;Acar A;Bayston L;Gildea C;Leverentz MK;Mills CG;Owens TW;Meurette O;Dorey K;Brennan K
Notch和Wnt是高度保守的信号通路，在动物发育过程中反复使用，以产生多种细胞类型。然而，它们通常对细胞命运决定具有相反的影响，每种途径都促进了替代结果。通常，接受两种信号的细胞仅表现出Wnt途径活性。这表明Wnt抑制Notch活性以促进Wnt-ON/Notch-OFF输出;但什么可能支持这种Notch调节尚不清楚。在这里，我们表明，Wnt的行为通过Dishevelled抑制Notch信号，这种串扰调节细胞命运的规格在体内非洲爪蟾的发展。在机制上，Dishevelled结合并直接抑制Notch受体下游的CSL转录因子，降低其活性。此外，我们的数据表明，这种串扰机制是保守的脊椎动物和无脊椎动物的同系物。因此，我们确定了Dishevelled作为Notch信号传导抑制剂和Wnt途径激活剂的双重功能，该双重功能使相反的Wnt和Notch反应之间的区别更加明显，从而允许稳健的细胞命运决定。
Notch and Wnt are highly conserved signalling pathways that are used repeatedly throughout animal development to generate a diverse array of cell types. However, they often have opposing effects on cell-fate decisions with each pathway promoting an alternate outcome. Commonly, a cell receiving both signals exhibits only Wnt pathway activity. This suggests that Wnt inhibits Notch activity to promote a Wnt-ON/Notch-OFF output; but what might underpin this Notch regulation is not understood. Here, we show that Wnt acts via Dishevelled to inhibit Notch signalling, and that this crosstalk regulates cell-fate specification in vivo during Xenopus development. Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhibitor of Notch signalling and an activator of the Wnt pathway that sharpens the distinction between opposing Wnt and Notch responses, allowing for robust cell-fate decisions.
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DOI：
10.1046/j.1432-1327.2001.02387.x
发表时间：
2001-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Fuchs, KP;Bommer, G;Kempkes, B
通讯作者：
Kempkes, B
影响因子：
4.6
作者：
Dahlqvist, C;Blokzijl, A;Lendahl, U
通讯作者：
Lendahl, U
DOI：
10.1023/b:jomg.0000037157.94207.33
发表时间：
2004-04-01
影响因子：
2.5
作者：
Brennan, KR;Brown, AMC
通讯作者：
Brown, AMC
影响因子：
23.9
作者：
Bouras, Toula;Pal, Bhupinder;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
11.8
作者：
Chalmers, AD;Welchman, D;Papalopulu, N
通讯作者：
Papalopulu, N