Asymmetric mechanotransduction by hair cells of the zebrafish lateral line (Part 2/2)

In the lateral line system, water motion is detected by neuromast organs,
fundamental units that are arrayed on a fish’s surface. Each neuromast
contains hair cells, specialized mechanoreceptors that convert mechanical
stimuli, in the form of water movement, into electrical signals. The
orientation of hair cells’ mechanosensitive structures ensures that the
opening of mechanically-gated channels is maximal when deflected in a
single direction. In each neuromast organ, hair cells have two opposing
orientations, enabling bi-directional detection of water movement.
Interestingly, Tmc2b and Tmc2a proteins, which constitute the
mechanotransduction channels in neuromasts, distribute asymmetrically so
that Tmc2a is expressed in hair cells of only one orientation. Here, using
both in vivo recording of extracellular potentials and calcium imaging of
neuromasts, we demonstrate that hair cells of one orientation have larger
mechanosensitive responses. The associated afferent neuron processes that
innervate neuromast hair cells faithfully preserve this functional
difference. Moreover, Emx2, a transcription factor required for the
formation of hair cells with opposing orientations, is necessary to
establish this functional asymmetry within neuromasts. Remarkably, loss of
Tmc2a does not impact hair cell orientation but abolishes the functional
asymmetry as measured by recording extracellular potentials and calcium
imaging. Overall, our work indicates that oppositely oriented hair cells
within a neuromast employ different proteins to alter mechanotransduction
to sense the direction of water motion.

在鱼类侧线系统（lateral line system）中，水体运动由排布于鱼体表面的基本功能单位——神经丘器官（neuromast organs）所感知。每个神经丘均包含毛细胞（hair cells）这类特化的机械感受器（mechanoreceptors），它们可将水体运动形式的机械刺激转换为电信号。毛细胞的机械敏感结构的定向特性，确保其机械门控通道（mechanically-gated channels）仅在向单一方向偏转时达到最大开放状态。每个神经丘器官内的毛细胞存在两种相反的定向模式，由此实现对水体运动的双向检测。
值得注意的是，构成神经丘机械转导通道的Tmc2b与Tmc2a蛋白呈不对称分布：Tmc2a仅在单一定向的毛细胞中表达。本研究通过对细胞外电位（extracellular potentials）的活体记录以及神经丘的钙成像（calcium imaging）实验，证实单一定向的毛细胞具有更强的机械敏感响应。支配神经丘毛细胞的相关传入神经元（afferent neuron）突起可忠实保留这一功能差异。此外，调控相反定向毛细胞形成的转录因子（transcription factor）Emx2，对于神经丘内功能不对称性的建立是必需的。值得注意的是，缺失Tmc2a并不会影响毛细胞的定向模式，但会消除通过细胞外电位记录与钙成像所观测到的功能不对称性。综上，本研究表明，神经丘内定向相反的毛细胞可通过利用不同蛋白来改变机械转导过程，从而实现对水体运动方向的感知。