Jacinto Raquel, Sampaio Pedro, Roxo-Rosa Mónica, Pestana Sara, Lopes Susana S
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
Front Cell Dev Biol. 2021 Apr 1;9:624531. doi: 10.3389/fcell.2021.624531. eCollection 2021.
The left-right (LR) field recognizes the importance of the mechanism involving the calcium permeable channel Polycystin-2. However, whether the early LR symmetry breaking mechanism is exclusively Polycystin-2 has not been tested. For that purpose, we need to be able to isolate the effects of decreasing the levels of Pkd2 protein from any eventual effects on flow dynamics. Here we demonstrate that () homozygous mutants have abnormal flow dynamics. In addition, we performed one cell stage Pkd2 knockdowns and LR organizer specific Pkd2 knockdowns and observed that both techniques resulted in shorter cilia length and abnormal flow dynamics. We conclude that Pkd2 reduction leads to LR defects that cannot be assigned exclusively to its putative role in mediating mechanosensation because indirectly, by modifying cell shape or decreasing cilia length, Pkd2 deficit affects LR flow dynamics.
左右（LR）领域认识到涉及钙通透性通道多囊蛋白-2的机制的重要性。然而，早期LR对称性破坏机制是否仅由多囊蛋白-2介导尚未得到验证。为此，我们需要能够将降低Pkd2蛋白水平的影响与对流体动力学的任何最终影响隔离开来。在这里，我们证明（）纯合突变体具有异常的流体动力学。此外，我们进行了单细胞阶段的Pkd2敲低和LR组织者特异性的Pkd2敲低，并观察到这两种技术都导致纤毛长度缩短和流体动力学异常。我们得出结论，Pkd2减少会导致LR缺陷，这些缺陷不能仅归因于其在介导机械感觉中的假定作用，因为通过间接改变细胞形状或缩短纤毛长度，Pkd2缺乏会影响LR流体动力学。
