Regulation of Proneural Wave Propagation Through a Combination of Notch-Mediated Lateral Inhibition and EGF-Mediated Reaction Diffusion
Regulation of Proneural Wave Propagation Through a Combination of Notch-Mediated Lateral Inhibition and EGF-Mediated Reaction Diffusion
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通过 Notch 介导的横向抑制和 EGF 介导的反应扩散相结合来调节前神经波传播
DOI：
10.1007/978-3-030-34436-8_5
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发表时间：
2020
影响因子：
--
通讯作者：
Yasugi Tetsuo
中科院分区：
文献类型：
--
作者：
Sato Makoto;Yasugi Tetsuo
Notch介导的侧抑制调节二元细胞命运选择，导致在各种生物过程中形成盐和胡椒图案。在许多情况下，Notch信号传导与其他信号传导系统一起起作用。然而，目前尚不清楚当Notch信号与其他信号系统结合时会发生什么。数学建模和使用一个简单的生物模型系统将是必不可少的，以解决这种不确定性。果蝇视觉中心的分化波，即“前神经波”，伴随着Notch和EGF信号通路的活动。尽管侧抑制所需的所有Notch信号成分都参与了前神经波，但在前神经波的进展过程中没有发现盐和胡椒图案。相反，Notch被沿着波前激活并调节前神经波的进展。Notch信号如何控制波的传播而不形成盐和胡椒图案？基于生物学证据的前神经波的数学模型已经证明，Notch介导的侧抑制在前神经波内实施，并且EGF的扩散作用取消了盐和胡椒图案的形成。数值模拟的结果已被体内遗传实验所证实，并表明Notch介导的侧抑制和EGF介导的反应扩散的组合使Notch信号传导的调节前神经波传播的新功能成为可能。类似的机制可能在动物发育和癌症发病机制中发现的各种生物学过程中发挥重要作用。
Notch-mediated lateral inhibition regulates binary cell fate choice, resulting in salt-and-pepper pattern formation during various biological processes. In many cases, Notch signaling acts together with other signaling systems. However, it is not clear what happens when Notch signaling is combined with other signaling systems. Mathematical modeling and the use of a simple biological model system will be essential to address this uncertainty. A wave of differentiation in theDrosophilavisual center, the “proneural wave,” accompanies the activity of the Notch and EGF signaling pathways. Although all of the Notch signaling components required for lateral inhibition are involved in the proneural wave, no salt-and-pepper pattern is found during the progression of the proneural wave. Instead, Notch is activated along the wave front and regulates proneural wave progression. How does Notch signaling control wave propagation without forming a salt-and-pepper pattern? A mathematical model of the proneural wave, based on biological evidence, has demonstrated that Notch-mediated lateral inhibition is implemented within the proneural wave and that the diffusible action of EGF cancels salt-and-pepper pattern formation. The results from numerical simulation have been confirmed by genetic experiments in vivo and suggest that the combination of Notch-mediated lateral inhibition and EGF-mediated reaction diffusion enables a novel function of Notch signaling that regulates propagation of the proneural wave. Similar mechanisms may play important roles in diverse biological processes found in animal development and cancer pathogenesis.