Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo
Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo
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DOI：
10.1038/s41467-019-12609-4
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发表时间：
2019-10-17
影响因子：
16.6
通讯作者：
Ishitani, Tohru
中科院分区：
文献类型：
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作者：
Akieda, Yuki;Ogamino, Shohei;Ishitani, Tohru
形态原信号传导形成一个活动梯度，并以信号强度依赖的方式指示细胞身份，以模式发育组织。然而，发育中的组织也会经历动态的形态发生，这可能会产生不合适的形态信号传导和随后的形态梯度嘈杂的细胞。在这里，我们展示了一个与细胞竞争相关的系统纠正了这种嘈杂的形态梯度。Wnt/ β -catenin信号梯度作为胚胎前后模式的形态形成因子，对斑马鱼的成像分析发现，具有异常Wnt/ β -catenin活性的不合适细胞会自发出现，并在梯度中产生噪声。不适应细胞和邻近适应细胞之间通过钙粘蛋白的交流通过激活Smad信号和活性氧的产生来刺激不适应细胞的凋亡。这种不合适的细胞消除是正确的Wnt/ β -连环蛋白梯度形成和随后的前后模式所必需的。因为这个梯度不仅控制胚胎的模式，也控制成人组织的模式，这个系统可能支持组织的健壮性和疾病预防。
Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/beta-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, identify that unfit cells with abnormal Wnt/beta-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/beta-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.