Steady-state invariant genetics: probing the role of morphogen gradient dynamics in developmental patterning.
Steady-state invariant genetics: probing the role of morphogen gradient dynamics in developmental patterning.
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稳态不变遗传学：探讨形态发生素梯度动力学在发育模式中的作用。
DOI：
10.1098/rsif.2010.0738
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Nahmad,Marcos
中科院分区：
文献类型：
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作者：
Nahmad,Marcos
在动物发育过程中，形态原介导的图案化是建立位置信息的主要机制。在经典观点中，位置信号的解释取决于形态根的平衡分布，而与梯度形成的动力学无关。形态原动力学是否有助于发育模式的问题还没有被详细探讨，部分原因是遗传实验选择性地影响信号动力学，同时保持稳定的形态原图谱不变，很难设计和解释。在这里，我提出了一种基于模型的方法来识别发育模式中可能影响瞬时信号梯度但保持稳定状态信号梯度不变的基因突变。作为一个案例研究，该方法被用来探索刺猬(HH)信号在果蝇翅膀发育过程中的动态特性。这一分析提供了如何在不影响HH浓度分布的稳态分布的情况下，对HH梯度动力学的不同属性(例如接触信号的持续时间或瞬时梯度的最大宽度)进行遗传扰动的洞察。我认为这种方法可以作为一种实验设计工具来研究瞬时形态梯度在发育模式中的作用，并讨论这些想法在其他问题上的普遍性。
Morphogen-mediated patterning is the predominant mechanism by which positional information is established during animal development. In the classical view, the interpretation of positional signals depends on the equilibrium distribution of a morphogen, regardless of the dynamics of gradient formation. The problem of whether or not morphogen dynamics contribute to developmental patterning has not been explored in detail, partly because genetic experiments, which selectively affect signalling dynamics while maintaining unchanged the steady-state morphogen profile, are difficult to design and interpret. Here, I present a modelling-based approach to identify genetic mutations in developmental patterning that may affect the transient, but leave invariant the steady-state signalling gradient. As a case study, this approach is used to explore the dynamic properties of Hedgehog (Hh) signalling in the developing wing of the fruitfly,Drosophila melanogaster. This analysis provides insights into how different properties of the Hh gradient dynamics, such as the duration of exposure to the signal or the maximum width of the transient gradient, can be genetically perturbed without affecting the steady-state distribution of the Hh concentration profile. I propose that this method can be used as an experimental design tool to investigate the role of transient morphogen gradients in developmental patterning and discuss the generality of these ideas in other problems.