Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo
Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo
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DOI：
10.1242/dev.009464
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发表时间：
2007-11-01
期刊：
影响因子：
4.6
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
--
作者：
Oki, Shinya;Hashimoto, Ryuju;Hamada, Hiroshi
小鼠的部位特异性器官发生是由于淋巴结腔内的液体向左侧流动，随后在侧板中胚层（LPM）左侧表达Nodal。该淋巴结的表达对于随后左侧LPM的不对称淋巴结表达至关重要，但该淋巴结产生的淋巴结的确切作用尚不清楚。我们现在研究了节点信号是如何从节点传递到LPM的。外部供应的Nodal蛋白未能向LPM发出信号，提示Nodal信号是通过内部途径而不是外部途径传递到LPM的。转基因拯救实验表明，节点共受体隐型（Cfc1）仅在LPM中而不是在LPM中表达不对称的节点，表明节点信号不是在节点和LPM之间间接传递的。在体外，Nodal与硫代糖胺聚糖（GAGs）相互作用，其特异性定位于小鼠胚胎中淋巴结和LPM之间的基底膜样结构。抑制硫酸酸化GAG生物合成可阻止LPM中Nodal的表达。这些数据表明，节点产生的Nodal可能通过与硫酸酸化的gag相互作用直接传递到LPM。
Situs- specific organogenesis in the mouse results from leftward fluid flow in the node cavity and subsequent left- sided expression of Nodal in the lateral plate mesoderm ( LPM). Nodal expression at the node is essential for the subsequent asymmetric Nodal expression in the left LPM, but the precise role of Nodal produced at the node has remained unknown. We have now investigated how the Nodal signal is transferred from the node to the LPM. Externally supplied Nodal protein failed to signal to the LPM, suggesting that the Nodal signal is transferred to the LPM via an internal route rather than an external one. Transgenic rescue experiments showed that the Nodal co- receptor Cryptic ( Cfc1) is required only in the LPM, not at the node, for asymmetric Nodal expression in the LPM, indicating that the Nodal signal is not relayed indirectly between the node and LPM. Nodal interacts in vitro with sulfated glycosaminoglycans ( GAGs), which are specifically localized to the basement membranelike structure between the node and LPM in the mouse embryo. Inhibition of sulfated GAG biosynthesis prevents Nodal expression in the LPM. These data suggest that Nodal produced at the node might travel directly to the LPM via interaction with sulfated GAGs.