A new mechanism for spatial pattern formation via lateral and protrusion-mediated lateral signalling.

A new mechanism for spatial pattern formation via lateral and protrusion-mediated lateral signalling.
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DOI:
10.1098/rsif.2016.0484
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发表时间:
2016-11
期刊:
Journal of the Royal Society, Interface
影响因子:
--
通讯作者:
Baum B
Baum B
中科院分区:
其他
文献类型:
--
作者:
Hadjivasiliou Z;Hunter GL;Baum B

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当遗传上相同的细胞呈现不同的命运时,组织组织和图案在发育过程中至关重要。横向信号在这一过程中起着重要的作用,它有助于在一个统一的细胞集合中产生自组织的空间模式。最近的数据表明,横向信号传导可以通过相邻细胞之间的连接接触和通过允许非相邻细胞在一定距离处相互作用的细胞突起来介导。然而,目前还不清楚这些不同类型的细胞-细胞接触介导的信号传导如何在没有可扩散的形态发生素或前模式的帮助下物理地促进复杂模式的产生。为了探讨这个问题,在这项工作中,我们开发了一个模型的基础上,一个单一的受体/配体对的Notch和Delta的横向信号。我们表明,允许信号动力学不同的交界处与adhersion介导的接触,一个假设的启发,最近的数据表明,切割的Notch在几个系统中需要δ结合和机械力的应用,允许单个细胞采取行动,以促进横向激活和横向抑制。引人注目的是,在这个模型下,Delta可以隔离Notch,观察到各种类似于反应扩散系统典型的模式,以及当我们考虑信号动力学变化时出现的更不寻常的模式,以及突起的长度和分布。重要的是,这些模式是自组织的,因此局部相互作用驱动组织规模的模式。总之,这些数据表明,原则上,突起除了有助于长距离信号传递和图案细化之外,还可以产生不同类型的图案。
Tissue organization and patterning are critical during development when genetically identical cells take on different fates. Lateral signalling plays an important role in this process by helping to generate self-organized spatial patterns in an otherwise uniform collection of cells. Recent data suggest that lateral signalling can be mediated both by junctional contacts between neighbouring cells and via cellular protrusions that allow non-neighbouring cells to interact with one another at a distance. However, it remains unclear precisely how signalling mediated by these distinct types of cell–cell contact can physically contribute to the generation of complex patterns without the assistance of diffusible morphogens or pre-patterns. To explore this question, in this work we develop a model of lateral signalling based on a single receptor/ligand pair as exemplified by Notch and Delta. We show that allowing the signalling kinetics to differ at junctional versus protrusion-mediated contacts, an assumption inspired by recent data which show that the cleavage of Notch in several systems requires both Delta binding and the application of mechanical force, permits individual cells to act to promote both lateral activation and lateral inhibition. Strikingly, under this model, in which Delta can sequester Notch, a variety of patterns resembling those typical of reaction–diffusion systems is observed, together with more unusual patterns that arise when we consider changes in signalling kinetics, and in the length and distribution of protrusions. Importantly, these patterns are self-organizing—so that local interactions drive tissue-scale patterning. Together, these data show that protrusions can, in principle, generate different types of patterns in addition to contributing to long-range signalling and to pattern refinement.
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