Vick Philipp, Kreis Jennifer, Schneider Isabelle, Tingler Melanie, Getwan Maike, Thumberger Thomas, Beyer Tina, Schweickert Axel, Blum Martin
Institute of Zoology, University of Hohenheim, 70599 Stuttgart, Germany.
Institute of Zoology, University of Hohenheim, 70599 Stuttgart, Germany.
iScience. 2018 Apr 27;2:76-85. doi: 10.1016/j.isci.2018.03.011. Epub 2018 Apr 7.
Nodal signaling controls asymmetric organ placement during vertebrate embryogenesis. Nodal is induced by a leftward fluid flow at the ciliated left-right organizer (LRO). The mechanism of flow sensing, however, has remained elusive. pkd2 encodes the calcium channel Polycystin-2, which is required for kidney development and laterality, and may act in flow perception. Here, we have studied the role of Polycystin-2 in Xenopus and show that pkd2 is indispensable for left-right (LR) asymmetry. Knockdown of pkd2 prevented left-asymmetric nodal cascade induction in the lateral plate mesoderm. Defects were due to failure of LRO specification, morphogenesis, and, consequently, absence of leftward flow. Polycystin-2 synergizes with the unconventional nodal-type signaling molecule Xnr3 to induce the LRO precursor tissue before gastrulation, upstream of symmetry breakage. Our data uncover an unknown function of pkd2 in LR axis formation, which we propose represents an ancient role of Polycystin-2 during LRO induction in lower vertebrates.
节点信号传导在脊椎动物胚胎发育过程中控制器官的不对称定位。节点由纤毛左右组织者（LRO）处的向左流体流动诱导产生。然而，流体感知机制仍然不清楚。多囊蛋白2基因（pkd2）编码钙通道多囊蛋白-2，其对于肾脏发育和左右不对称性是必需的，并且可能在流体感知中发挥作用。在这里，我们研究了多囊蛋白-2在非洲爪蟾中的作用，并表明pkd2对于左右（LR）不对称性是不可或缺的。敲低pkd2可阻止侧板中胚层中左侧不对称节点级联反应的诱导。缺陷是由于LRO特化、形态发生失败，以及因此导致的向左流体流动缺失所致。在原肠胚形成之前，在对称性打破的上游，多囊蛋白-2与非常规的节点型信号分子Xnr3协同作用，诱导LRO前体组织。我们的数据揭示了pkd2在LR轴形成中的未知功能，我们认为这代表了多囊蛋白-2在低等脊椎动物LRO诱导过程中的古老作用。
