Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors
Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors
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DOI：
10.1016/j.ydbio.2009.11.013
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发表时间：
2010-01-15
影响因子：
2.7
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
--
作者：
Ikeya, Makoto;Fukushima, Kumi;Sasai, Yoshiki
BMP信号的微调对于复杂器官发生的许多方面至关重要。在这份报告中，我们表明，BMP结合分泌因子，Crossveinless 2（Cv 2）的BMP信号的增强，是必不可少的哺乳动物肾单位的早期胚胎发育。在Cv 2基因敲除小鼠中，帽状凝聚物（通常表达Cv 2的肾单位祖细胞簇）的数量减少，并且凝聚物细胞表现出降低的聚集水平。在这些Cv 2（-/-）缩合物中，磷酸化Smad 1（pSmad 1）的水平显著降低。Cv 2（-/-）小鼠中Bmp 7等位基因的缺失增强了帽冷凝物缺陷，并进一步降低了该组织中pSmad 1的水平。这些观察结果表明，Cv 2在早期肾发生中具有pro-BMP功能。有趣的是，Cv 2（-/-）突变体的肾缺陷被扭曲原肠胚形成（Tsg）的无效突变完全抑制，其编码另一种BMP结合因子，表明Cv 2依赖Tsg发挥其促BMP肾生成功能。通过使用胚胎肾细胞系，我们提出的实验证据表明，Cv 2增强Tsg的pro-BMP活性。这些发现揭示了细胞外修饰剂之间的分子层次结构，这些修饰剂在器官发生微环境中协调局部BMP信号峰。(C)2009 Elsevier Inc. All rights reserved.
The fine-tuning of BMP signals is critical for many aspects of complex organogenesis. In this report, we show that the augmentation of BMP signaling by a BMP-binding secreted factor, Crossveinless2 (Cv2), is essential for the early embryonic development of mammalian nephrons. In the Cv2-null mouse, the number of cap condensates (clusters of nephron progenitors, which normally express Cv2) was decreased, and the condensate cells exhibited a reduced level of aggregation. In these Cv2(-/-) condensates, the level of phosphorylated Smad1 (pSmad1) was substantially lowered. The loss of a Bmp7 allele in the Cv2(-/-) mouse enhanced the cap condensate defects and further decreased the level of pSmad1 in this tissue. These observations indicated that Cv2 has a pro-BMP function in early nephrogenesis. Interestingly, the renal defects of the Cv2(-/-) mutant were totally suppressed by a null mutation of Twisted gastrulation (Tsg), which encodes another BMP-binding factor, showing that Cv2 exerts its pro-BMP nephrogenic function Tsg-dependently. By using an embryonic kidney cell line, we presented experimental evidence showing that Cv2 enhances pro-BMP activity of Tsg. These findings revealed the molecular hierarchy between extracellular modifiers that orchestrate local BMP signal peaks in the organogenetic microenvironment. (C) 2009 Elsevier Inc. All rights reserved.