TGF-β signaling inhibits canonical BMP signaling pathway during palate development.
TGF-β signaling inhibits canonical BMP signaling pathway during palate development.
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TGF-β 信号传导抑制上颚发育过程中的经典 BMP 信号传导途径
DOI：
10.1007/s00441-017-2757-y
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发表时间：
2018-03
影响因子：
3.6
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Yuan G;Zhan Y;Gou X;Chen Y;Yang G
在早期腭发育过程中，基因表达和调控表现出沿着前后轴的异质性。转化生长因子-β（Transforming growth factor-β，TGF-β）和骨形态发生蛋白（bone morphogenetic protein，BMP）信号通路在腭的发育过程中起重要作用，但二者之间的确切关系尚不清楚。在这里，我们表明，在早期的次生腭发育，磷酸-（P）Smad 1/5/8是高度表达的前腭，但相对较低的表达在后腭。相反，pSmad 2/3在前腭中的表达水平低于后腭。利用BRE-Gal报告基因，我们发现经典的BMP信号通路在前腭中没有被激活，但在后腭中表现出中等水平。免疫共沉淀显示，Smad 4结合pSmad 1/5/8只在后腭，而不是在前腭。敲除腭间充质中的Tgfbr 2（Wnt 1-Cre; Tgfbr 2f/f;BRE）增强了后腭中而不是前腭中的典型BMP活性，因为pSmad 2/3降低。pSmad 1/5/8-Smad 4复合物被发现显着增加后腭间充质细胞在胚胎第13.5天，在SB 525334的存在下培养。邻位连接实验也显示pSmad 1/5/8-Smad 4复合物在Wnt 1-Cre; Tgfbr 2f/f小鼠后腭中增加。因此，Wnt 1-Cre; Tgfbr 2f/f;BRE小鼠腭间充质中pSmad 2/3水平的降低主要有助于pSmad 1/5/8-Smad 4复合物的增加，从而导致后腭中典型BMP活性的增强。此外，在早期发育过程中，典型的BMP信号在后腭运作，但在前腭完全不存在。典型的TGF-β信号通过竞争有限的Smad 4抑制后腭中典型的BMP信号活性。
During early palate development, gene expression and regulation exhibit heterogeneity along the anterior-posterior axis. Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play essential roles in secondary palatal formation but the exact relationship between the TGF-β and BMP pathways in palate development remains unknown. Here, we demonstrate that, during early secondary palate development, phospho-(p)Smad1/5/8 is highly expressed in the anterior palate but relatively lowly expressed in the posterior palate. Conversely, pSmad2/3 has a lower expression level in the anterior palate than in the posterior palate. With the BRE-Gal reporter, we found that the canonical BMP signaling pathway was not activated in the anterior palate but exhibited a moderate level in the posterior palate. Co-immunoprecipitation revealed that Smad4 bound to pSmad1/5/8 only in the posterior palate and not in the anterior palate. Knocking-out of Tgfbr2 (Wnt1-Cre;Tgfbr2f/f;BRE) in the palatal mesenchyme enhanced canonical BMP activity in the posterior palate but not in the anterior palate, because of decreased pSmad2/3. pSmad1/5/8-Smad4 complexes were found to be dramatically increased in posterior palatal mesenchymal cells at embryonic day 13.5 cultured in the presence of SB525334. Proximity ligation assay also showed pSmad1/5/8-Smad4 complexes were increased in the posterior palate of Wnt1-Cre;Tgfbr2f/f mice. Therefore, the reduction of pSmad2/3 level in the palatal mesenchyme of Wnt1-Cre;Tgfbr2f/f;BRE mice contributes primarily to the increase of pSmad1/5/8-Smad4 complexes leading to enhanced canonical BMP activity in the posterior palate. Moreover, during early development, canonical BMP signaling operates in the posterior palate but is completely absent in the anterior palate. Canonical TGF-β signaling suppresses canonical BMP signaling activity in the posterior palate by competing limited Smad4.
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影响因子：
1.5
作者：
Chytil, A;Magnuson, MA;Moses, HL
通讯作者：
Moses, HL
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