Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, AP-HP, Institut du Cerveau et de la Moelle épinière (ICM) - Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Nat Commun. 2018 Sep 18;9(1):3804. doi: 10.1038/s41467-018-06225-x.
Defects in cerebrospinal fluid (CSF) flow may contribute to idiopathic scoliosis. However, the mechanisms underlying detection of CSF flow in the central canal of the spinal cord are unknown. Here we demonstrate that CSF flows bidirectionally along the antero-posterior axis in the central canal of zebrafish embryos. In the cfap298 mutant, reduction of cilia motility slows transport posteriorly down the central canal and abolishes spontaneous activity of CSF-contacting neurons (CSF-cNs). Loss of the sensory Pkd2l1 channel nearly abolishes CSF-cN calcium activity and single channel opening. Recording from isolated CSF-cNs in vitro, we show that CSF-cNs are mechanosensory and require Pkd2l1 to respond to pressure. Additionally, adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, reminiscent of kyphosis in humans. These results indicate that CSF-cNs are mechanosensory cells whose Pkd2l1-driven spontaneous activity reflects CSF flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to maintenance of natural curvature of the spine.
脑脊液（CSF）流动缺陷可能导致特发性脊柱侧凸。然而，目前尚不清楚检测脊髓中央管内 CSF 流动的机制。在这里，我们证明 CSF 在斑马鱼胚胎的中央管中沿前后轴双向流动。在 cfap298 突变体中，纤毛运动减少会减缓 CSF 在后向中央管中的运输，并消除 CSF 接触神经元（CSF-cN）的自发性活动。感觉 Pkd2l1 通道的缺失几乎消除了 CSF-cN 的钙活性和单通道开放。在体外分离的 CSF-cN 记录中，我们表明 CSF-cN 是机械敏感的，需要 Pkd2l1 来响应压力。此外，成年 pkd2l1 突变体斑马鱼会出现脊柱曲率过度增加，类似于人类的脊柱后凸。这些结果表明，CSF-cN 是机械敏感细胞，其 Pkd2l1 驱动的自发性活动反映了体内 CSF 流动。此外，CSF-cN 中的 Pkd2l1 有助于维持脊柱的自然曲率。
