Modeling pattern formation in hydra: a route to understanding essential steps in development

Modeling pattern formation in hydra: a route to understanding essential steps in development
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DOI:
10.1387/ijdb.113483hm
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发表时间:
2012-01-01
影响因子:
0.7
通讯作者:
Meinhardt, Hans
Meinhardt, Hans
中科院分区:
生物学4区
文献类型:
--
作者:
Meinhardt, Hans

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水螅模式形成的建模揭示了复杂和自我调节模式可重复产生的基本机制。组织区域可以通过局部自我增强反应产生,该反应与较长范围的抑制作用相结合。这样的反应使得即使在最初几乎均匀的细胞组装中也能够形成图案。组织者对进行模式形成反应的能力的长期反馈在生长期间稳定了极轴模式,并允许在保留极性的情况下再生。假设Hypostome的形成是在两个正反馈回路的控制下,其中Wnt 3是一个共同的元素。除了使用β-连环蛋白的已建立的环之外,还涉及第二个细胞局部环,可能具有Brachyury作为额外的组分。该模型解释了β-连环蛋白和Wnt 3的不同表达模式。Wnt分子被认为发挥双重作用,作为激活剂,并在加工后作为抑制剂。由于Wnt基因编码完整的模式形成系统,基因复制和多样化导致一个基因家族,其表达区域彼此之间具有精确的关系。触手形成是通过初级系统施加的中等范围激活和局部排斥来定位第二模式形成系统的例子。芽形成的模型表明,一个短暂的芽前信号参与启动形成的脚的芽,接近正常的脚,以及接近芽尖。在经典和分子观测中观察到的许多动态调节在计算机模拟中再现。水螅可以被视为一种活化石,记录了在躯干形成和双侧性被发明之前的进化早期轴的形成。本文件所附补充资料中有动画模拟。
Modeling of pattern formation in hydra has revealed basic mechanisms that underlie the reproducible generation of complex and self-regulating patterns. Organizing regions can be generated by a local self-enhancing reaction that is coupled with an inhibitory effect of longer range. Such reactions enable pattern formation even in an initially almost homogeneous assembly of cells. A long-ranging feedback of the organizer onto the competence to perform the pattern-forming reaction stabilizes the polar axial pattern during growth and allows for regeneration with preserved polarity. Hypostome formation is assumed to be under the control of two positive feedback loops in which Wnt3 is a common element. In addition to the well-established loop employing beta-catenin, a second cell-local loop is involved, possibly with Brachyury as an additional component. This model accounts for the different expression patterns of beta-catenin and Wnt3. Wnt molecules are proposed to play a dual role, functioning as activators and, after processing, as inhibitors. Since Wnt genes code for complete pattern-forming systems, gene duplication and diversification lead to a family of genes whose expression regions have a precise relation to each other. Tentacle formation is an example of positioning a second pattern-forming system by medium-ranging activation and local exclusion exerted by the primary system. A model for bud formation suggests that a transient pre-bud signal is involved that initiates the formation of the foot of the bud, close to the normal foot, as well as close to the bud tip. Many dynamic regulations, as observed in classical and molecular observations, are reproduced in computer simulations. A case is made that hydra can be regarded as a living fossil, documenting an evolutionary early axis formation before trunk formation and bilaterality were invented. Animated simulations are available in the supplementary information accompanying this paper.