Wnt/Dkk Negative Feedback Regulates Sensory Organ Size in Zebrafish
Wnt/Dkk Negative Feedback Regulates Sensory Organ Size in Zebrafish
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DOI：
10.1016/j.cub.2013.06.035
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发表时间：
2013-08
期刊：
影响因子：
9.2
通讯作者：
H. Wada;A. Ghysen;K. Asakawa;Gembu Abe;Tohru Ishitani;K. Kawakami
中科院分区：
文献类型：
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作者：
H. Wada;A. Ghysen;K. Asakawa;Gembu Abe;Tohru Ishitani;K. Kawakami
正确的器官大小必须涉及细胞增殖的促进和抑制之间的平衡。已经提出了一个数学模型，其中假设器官产生自己的生长激活剂和生长抑制剂[1]，但尚未有分子证据支持该模型[2]。鱼侧线系统的机械感觉器官（神经丘）由感觉毛细胞核心组成，周围环绕着非感觉支持细胞。感觉细胞不断被替换，并从周围的非感觉细胞再生[3]，而每个器官在整个生命过程中都保持相同的大小。此外，神经丘还会长出新的神经丘，当它们达到相同大小时就会停止生长 [4, 5]。在这里，我们发现神经丘的大小是由具有增殖能力的细胞中促进生长的 Wnt 信号活性与分化的感觉细胞产生的 Wnt 抑制 Dkk 活性之间的平衡控制的。 Dkk（由分化细胞分泌）对 Wnt 依赖性细胞增殖（在周围细胞中）的这种负反馈循环也在再生过程中发挥作用，以实现尺寸恒定。这项研究将 Wnt/Dkk 确立为一种确定器官最终大小的新机制。
Correct organ size must involve a balance between promotion and inhibition of cell proliferation. A mathematical model has been proposed in which an organ is assumed to produce its own growth activator as well as a growth inhibitor [1], but there is as yet no molecular evidence to support this model [2]. The mechanosensory organs of the fish lateral line system (neuromasts) are composed of a core of sensory hair cells surrounded by nonsensory support cells. Sensory cells are constantly replaced and are regenerated from surrounding nonsensory cells [3], while each organ retains the same size throughout life. Moreover, neuromasts also bud off new neuromasts, which stop growing when they reach the same size [4, 5]. Here, we show that the size of neuromasts is controlled by a balance between growth-promoting Wnt signaling activity in proliferation-competent cells and Wnt-inhibiting Dkk activity produced by differentiated sensory cells. This negative feedback loop from Dkk (secreted by differentiated cells) on Wnt-dependent cell proliferation (in surrounding cells) also acts during regeneration to achieve size constancy. This study establishes Wnt/Dkk as a novel mechanism to determine the final size of an organ.