Syndecan4 coordinates Wnt/JNK and BMP signaling to regulate foregut progenitor development.
Syndecan4 coordinates Wnt/JNK and BMP signaling to regulate foregut progenitor development.
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Syndecan4 协调 Wnt/JNK 和 BMP 信号传导以调节前肠祖细胞发育。
DOI：
10.1016/j.ydbio.2016.05.025
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发表时间：
2016
影响因子：
2.7
通讯作者：
Zorn,AaronM
中科院分区：
文献类型：
--
作者：
Zhang,Zheng;Rankin,ScottA;Zorn,AaronM
时间和空间动态 Wnt 和 BMP 信号对于形成肝脏、胰腺和肺的前肠内胚层祖细胞模式至关重要，但这两种信号通路如何在细胞外空间协调尚不清楚。在这里，我们确定了跨膜硫酸乙酰肝素蛋白聚糖 Syndecan-4 (Sdc4)，它是非洲爪蟾前肠中非典型 Wnt 和 BMP 信号传导的关键调节因子。前肠特异性 Sdc4 耗竭会导致纤连蛋白 (Fn1) 基质破坏、细胞粘附减少以及无法维持前肠基因表达，最终导致前肠器官发育不全。 Sdc4 需要在hhex+前肠祖细胞中维持强大的 Wnt/JNK 和 BMP/Smad1 信号传导。通路分析表明，Sdc4 与 Fzd7 功能性相互作用，促进 Wnt/JNK 信号传导，从而维持前肠身份和细胞粘附。此外，Sdc4 胞外域需要支持 Fn1 基质组装，这对于促进前肠基因表达的强大 BMP 信号传导至关重要。这项工作揭示了细胞外基质如何在器官发生过程中协调不同的信号通路。
Temporally and spatially dynamic Wnt and BMP signals are essential to pattern foregut endoderm progenitors that give rise to the liver, pancreas and lungs, but how these two signaling pathways are coordinated in the extracellular space is unknown. Here we identify the transmembrane heparan sulphate proteoglycan Syndecan-4 (Sdc4), as a key regulator of both non-canonical Wnt and BMP signaling in theXenopusforegut. Foregut-specific Sdc4 depletion results in a disrupted Fibronectin (Fn1) matrix, reduced cell adhesion, and failure to maintain foregut gene expression ultimately leading to foregut organ hypoplasia. Sdc4 is required to maintain robust Wnt/JNK and BMP/Smad1 signaling in thehhex+foregut progenitors. Pathway analysis suggests that Sdc4 functionally interacts with Fzd7 to promote Wnt/JNK signaling, which maintains foregut identity and cell adhesion. In addition, the Sdc4 ectodomain is required to support Fn1 matrix assembly, which is essential for the robust BMP signaling that promotes foregut gene expression. This work sheds lights on how the extracellular matrix can coordinate different signaling pathways during organogenesis.