中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (12): 1901-1905.doi: 10.4103/1673-5374.165216

• 观点:神经损伤修复保护与再生 •    下一篇

针对细胞形态和记忆形成的一种再生模式模型

  

  • 收稿日期:2015-07-24 出版日期:2015-12-30 发布日期:2015-12-30

Target morphology and cell memory: a model of regenerative pattern formation

Nikolai Bessonov1, Michael Levin2, Nadya Morozova3, 4, Natalia Reinberg1, Alen Tosenberger4, 5, Vitaly Volpert6, *   

  1. 1 Institute of Problems of Mechanical Engineering, Russian Academy of Sciences, 199178 Saint Petersburg, Russia
    2 Department of Biology, Tufts Center for Regenerative & Developmental Biology, Tufts University, Medford, MA, USA
    3 Laboratoire Epigénétique et Cancer, CNRS FRE 3377, CEA Saclay, France
    4 Institut des Hautes Etudes Scientiques, 91440 Bures-sur-Yvette, France
    5 Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, CP 231, Brussels B-1050, Belgium
    6 Institut Camille Jordan, UMR 5208 CNRS, University Lyon 1, 69622 Villeurbanne, France
  • Received:2015-07-24 Online:2015-12-30 Published:2015-12-30
  • Contact: Vitaly Volpert, Ph.D.,volpert@math.univ-lyon1.fr.
  • About author:ML is grateful for the support of the G. Harold and Leila Y. Mathers Charitable Foundation, the Templeton World Charity Foundation (TWCF0089/AB55), and the W.M. Keck Foundation.

摘要:

许多生物有机体可以再生他们的一些组织和器官。一些物种,如水螅或真涡虫,可以从其一小部分再生出整个有机体。其他生物,如山椒,可以再生肢体、眼、脑的各部分以及脊髓和爪部等。而哺乳动物的再生潜力却十分有限,包括伤口愈合,以及一些复杂结构的再生,如肝脏,儿童指尖等。通过对涡虫再生进行的实验证明组织可以保留自己状态前的一些信息。当被等分时,蠕虫前端产生一个头,而后侧片产生一个尾巴。因此,很明显,伤口部位决定其身体部位是否可以再生或能否在局部发生。蠕虫成体干细胞必须从远端身体部位整合信息,进而了解丢失了什么部分,伤口位于哪里。文中针对实验模型揭示了一个方案,该方案将说明如何存储稳定再生方案,并重新写入蜂窝细胞网络中。今后的努力方向是将模型扩展到目标形态变化的其他例子。基于代理模式融合的模式记忆和连续梯度模型,将为临床提供急需的理论指导和实验记忆模式。

Abstract:

Despite the growing body of work on molecular components required for regenerative repair, we still lack a deep understanding of the ability of some animal species to regenerate their appropriate complex anatomical structure following damage. A key question is how regenerating systems know when to stop growth and remodeling – what mechanisms implement recognition of correct morphology that signals a stop condition? In this work, we review two conceptual models of pattern regeneration that implement a kind of pattern memory. In the first one, all cells communicate with each other and keep the value of the total signal received from the other cells. If a part of the pattern is amputated, the signal distribution changes. The difference fromthe original signal distribution stimulates cell proliferation and leads to pattern regeneration, in effect implementing an error minimization process that uses signaling memory to achieve pattern correction. In the second model, we consider a more complex pattern organization with different cell types. Each tissue contains a central (coordinator) cell that controls the tissue and communicates with the other central cells. Each of them keeps memory about the signals received from other central cells. The values of these signals depend on the mutual cell location, and the memory allows regeneration of the structure when it is modified. The purpose of these models is to suggest possible mechanisms of pattern regeneration operating on the basis of cell memory which are compatible with diverse molecular implementation mechanisms within specific organisms.

Key words: target morphology, pattern regeneration, cell memory, morphogenesis, cell signaling, mathematical modeling, agent-based model