Okada Yasushi, Takeda Sen, Tanaka Yosuke, Belmonte Juan-Carlos Izpisúa, Hirokawa Nobutaka
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037.
Cell. 2005 May 20;121(4):633-644. doi: 10.1016/j.cell.2005.04.008.
The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases, primary monocilia present a clockwise rotational-like motion. Observations of defective ciliary dynamics in mutant mouse embryos support the idea that the posterior tilt of the cilia during rotational-like beating can explain the leftward fluid flow. Moreover, we show that this leftward flow may produce asymmetric distribution of exogenously introduced proteins, suggesting morphogen gradients as a subsequent mechanism of left-right axis determination. Finally, we experimentally and theoretically characterize under which conditions a morphogen gradient can arise from the flow.
胚外液向左流动对于小鼠胚胎左右轴的初始确定至关重要。目前尚不清楚这是否是其他脊椎动物中的保守机制，以及这种流动的方向性是如何由纤毛运动产生的。在本文中，我们表明兔和青鳉胚胎的腹侧节点也表现出向左的液流。在所有情况下，初级单纤毛呈现出顺时针旋转样运动。对突变小鼠胚胎中纤毛动力学缺陷的观察支持了这样一种观点，即纤毛在旋转样摆动期间的后倾可以解释向左的液流。此外，我们表明这种向左流动可能会导致外源引入蛋白质的不对称分布，这表明形态发生素梯度是左右轴确定的后续机制。最后，我们通过实验和理论表征了在何种条件下可以从流动中产生形态发生素梯度。
