Lack of a laterality phenotype in Pkd1 knock-out embryos correlates with absence of polycystin-1 in nodal cilia
Lack of a laterality phenotype in Pkd1 knock-out embryos correlates with absence of polycystin-1 in nodal cilia
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DOI：
10.1111/j.1432-0436.2005.00048.x
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发表时间：
2005-10-01
期刊：
影响因子：
2.9
通讯作者：
Blum, M
中科院分区：
文献类型：
--
作者：
Karcher, C;Fischer, A;Blum, M
在脊椎动物中，胸腹器官的不对称分布是由胚胎发生过程中节点信号级联的左不对称活动控制的。在小鼠胚胎中，淋巴结的不对称诱导被认为依赖于腹侧淋巴结细胞上的功能性单纤毛和编码钙通道多囊蛋白-2 （PC2）的Pkd2基因。在人类中，PKD2和PKD1的突变引起多囊肾病。PC1和PC2蛋白被认为是多因子复合体的一部分。这两种蛋白在原发性肾纤毛上的定位表明其对腹侧淋巴结纤毛有作用。我们研究了Pkd1敲除胚胎的侧边性缺陷，发现野生型器官形态发生和正常表达nodal和Pitx2。虽然PC2定位于结节纤毛，但在小鼠胚胎中未检测到PC1的纤毛定位。这一发现在一种典型的哺乳动物胚盘——兔胚胎中得到了证实。因此，在Pkd1敲除的胚胎中，缺乏PC1定位到纤毛与缺乏侧边缺陷相对应。我们的研究结果表明，PC2在左右轴形成过程中具有pc1独立的功能，并间接支持PC2在这一过程中的纤毛作用。
The invariant asymmetric placement of thoracic and abdominal organs in the vertebrates is controlled by the left-asymmetric activity of the Nodal signaling cascade during embryogenesis. In the mouse embryo asymmetric induction of nodal is thought to be dependent on functional monocilia on the ventral node cells and on the Pkd2 gene, which encodes the calcium channel polycystin-2 (PC2). In humans mutations in PKD2 and PKD1 give rise to polycystic kidney disease. The PC1 and PC2 proteins are thought to function as part of a multifactorial complex. Localization of both proteins to the primary renal cilium suggested a function on cilia of the ventral node. Here we investigated Pkd1 knock-out embryos for laterality defects and found wild-type organ morphogenesis and normal expression of nodal and Pitx2. While PC2 localized to nodal cilia, no ciliary localization of PC1 was detected in mouse embryos. This finding was confirmed in an archetypical mammalian blastodisc, the rabbit embryo. Thus, absence of PC1 localization to cilia corresponded with a lack of laterality defects in Pkd1 knock-out embryos. Our results demonstrate a PC1-independent function of PC2 in left-right axis formation, and indirectly support a ciliary role of PC2 in this process.