EphB2 and EphB3 forward signalling are required for palate development
EphB2 and EphB3 forward signalling are required for palate development
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DOI：
10.1016/j.mod.2008.10.009
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发表时间：
2009-03-01
影响因子：
2.6
通讯作者：
McLean, William
中科院分区：
文献类型：
--
作者：
Risley, Michael;Garrod, David;McLean, William
Eph 和肝配蛋白是细胞表面受体，它们相互结合并在称为前向 (Eph) 和反向 (肝配蛋白) 信号传导的过程中启动不同的双向信号传导途径。先前的研究表明，ephrinB1 蛋白单独缺失或 EphB2 和 EphB3 复合缺失会导致腭裂。由于这些分子的双向信号传导能力，尚不清楚是正向还是反向信号传导导致 ephrinB1 蛋白缺失或 EphB2 和 EphB3 化合物缺失小鼠出现腭裂。我们证明前向信号对于腭发育至关重要。具有细胞质截短的 EphB2 蛋白的胎儿患有腭裂，该蛋白可以启动反向信号但不能启动正向信号传导，并且 EphB3 蛋白无效。发生这种情况是因为它们的腭架太小而无法相互接触，而腭架可以在体内升高并在培养物中粘附和融合。架子尺寸小是由于腭间充质增殖减少所致。增殖减少并不是腭内血管发育异常的结果。总之，为 EphB2 和 EphB3 在上颚发育中的特定和协同作用提供了强有力的证据。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Ephs and ephrins are cell surface receptors that bind to each other and initiate distinct, bidirectional signalling pathways in processes known as forward (Eph) and reverse (ephrin) signalling. Previous work had shown that the loss of ephrinB1 protein alone or compound loss of EphB2 and EphB3 leads to cleft palate. Because of the bidirectional signalling capability of these molecules, it was not clear whether forward or reverse signalling caused the cleft palate in the ephrinB1 protein null or EphB2 and EphB3 compound null mice. We demonstrate that forward signalling is essential for palatogenesis. Foetuses with a cytoplasmically truncated EphB2 protein, which could initiate reverse but not forward signalling, and were protein null for EphB3 had a cleft palate. This happened because their palatal shelves, which could elevate in vivo and adhere and fuse in culture, were too small to contact one another. Small shelf size was due to reduced proliferation in the palatal mesenchyme. The reduced proliferation was not the result of abnormal vascular development within the palate. In conclusion, strong evidence is provided for specific and co-operative roles of EphB2 and EphB3 in palate development. (C) 2008 Elsevier Ireland Ltd. All rights reserved.