Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points
Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points
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DOI：
10.1016/j.ydbio.2007.03.001
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发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Bakkers, Jeroen
中科院分区：
文献类型：
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作者：
Chocron, Sonja;Verhoeven, Manon C.;Bakkers, Jeroen
左右（LR）不对称是由胚胎内的早期不对称信号调节的。尽管骨形态发生蛋白（BMP）通路在这一过程中的作用已经在各种模式生物中被广泛报道，但关于BMP信号传导机制的相反模型仍然盛行。在这里，我们表明在斑马鱼胚胎中，在LR模式中有两个不同的阶段需要BMP信号。利用异位表达noggin3或bmp2b的转基因细胞系，我们发现在早期分节过程中需要BMP信号传导来抑制右外侧板中胚层的左爪表达，并调节内脏和心脏侧向。第二阶段是在分节后期发现的，此时左侧外侧板中胚层需要BMP信号来调节左侧基因表达和心脏侧度。通过morpholino敲除实验，我们确定Bmp4是负责BMP信号传导两个阶段的配体。此外，我们检测到bmp4在库普弗氏囊泡中的表达，并表明该结构中bmp4的限制性敲低导致LR模式缺陷。这两种截然不同的BMP信号活动的识别为BMP信号如何调节LR模式提供了新的见解。(c) 2007爱思唯尔公司版权所有。
Left-right (LR) asymmetry is regulated by early asymmetric signals within the embryo. Even though the role of the bone morphogenetic protein (BMP) pathway in this process has been reported extensively in various model organisms, opposing models for the mechanism by which BMP signaling operates still prevail. Here we show that in zebrafish embryos there are two distinct phases during LR patterning in which BMP signaling is required. Using transgenic lines that ectopically express either noggin3 or bmp2b, we show a requirement for BMP signaling during early segmentation to repress southpaw expression in the right lateral plate mesoderm and regulate both visceral and heart laterality. A second phase was identified during late segmentation, when BMP signaling is required in the left lateral plate mesoderm to regulate left-sided gene expression and heart laterality. Using morpholino knock down experiments, we identified Bmp4 as the ligand responsible for both phases of BMP signaling. In addition, we detected bmp4 expression in Kupffer's vesicle and show that restricted knock down of bmp4 in this structure results in LR patterning defects. The identification of these two distinct and opposing activities of BMP signaling provides new insight into how BMP signaling can regulate LR patterning. (c) 2007 Elsevier Inc. All rights reserved.