Immotile cilia of the mouse node sense a fluid flow?induced mechanical force for left-right symmetry breaking
Immotile cilia of the mouse node sense a fluid flow?induced mechanical force for left-right symmetry breaking
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小鼠节点不动的纤毛感知流体流动引起的左右对称性破坏的机械力
DOI：
10.1101/2022.04.11.487968
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Hamada Hiroshi
中科院分区：
文献类型：
--
作者：
Katoh Takanobu A.;Omori Toshihiro;Mizuno Katsutoshi;Sai Xiaorei;Minegishi Katsura;Ikawa Yayoi;Nishimura Hiromi;Itabashi Takeshi;Kajikawa Eriko;Hiver Sylvain;Iwane Atsuko H.;Ishikawa Takuji;Okada Yasushi;Nishizaka Takayuki;Hamada Hiroshi
小鼠胚胎结节上的冠状细胞需要不动的纤毛，才能感觉到向左的流体流动，导致左-右(L-R)对称性的破坏。然而，长期以来，流动传感机制一直难以捉摸，机械传感和化学传感模型都已被提出。在这里，我们展示了小鼠结节的不动纤毛对机械力的反应。在向左血流的情况下，左侧的静止纤毛向腹侧弯曲，而右侧的纤毛向背侧弯曲。通过光钳对沿着背腹轴的静止纤毛施加机械刺激，在靶细胞中诱导了钙瞬变和Dand5mRNA的降解--这是第一个已知的L-R不对称分子事件。发现PKD2通道蛋白优先定位于结节左右两侧静止纤毛的背侧，机械刺激向腹侧优先诱导Ca~(2+)瞬变可以解释静止纤毛对定向流动的不同反应。因此，我们的结果表明，节点处的不动纤毛以一种依赖于流体产生的机械力的方式感知流体流动的方向。
Immotile cilia of crown cells at the node of mouse embryos are required for sensing of a leftward fluid flow that gives rise to the breaking of left-right (L-R) symmetry. The flow-sensing mechanism has long remained elusive, however, with both mechanosensing and chemosensing models having been proposed, –. Here we show that immotile cilia at the mouse node respond to mechanical force. In the presence of a leftward flow, immotile cilia on the left side of the node bend toward the ventral side whereas those on the right side bend toward the dorsal side. Application of mechanical stimuli to immotile cilia along the dorsoventral axis by optical tweezers induced Ca2+transients and degradation ofDand5mRNA—the first known L-R asymmetric molecular events—in the targeted cells. The Pkd2 channel protein was found to be preferentially localized to the dorsal side of immotile cilia on both left and right sides of the node, and the observed induction of Ca2+transients preferentially by mechanical stimuli directed toward the ventral side could explain the differential response of immotile cilia to the directional flow. Our results thus suggest that immotile cilia at the node sense the direction of fluid flow in a manner dependent on a flow-generated mechanical force.