McLaughlin Todd, O'Leary Dennis D M
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Annu Rev Neurosci. 2005;28:327-55. doi: 10.1146/annurev.neuro.28.061604.135714.
Gradients of axon guidance molecules have long been postulated to control the development of the organization of neural connections into topographic maps. We review progress in identifying molecules required for mapping and the mechanisms by which they act, focusing on the visual system, the predominant model for map development. The Eph family of receptor tyrosine kinases and their ligands, the ephrins, remain the only molecules that meet all criteria for graded topographic guidance molecules, although others fulfill some criteria. Recent reports further define their modes of action and new roles for them, including EphB/ephrin-B control of dorsal-ventral mapping, bidirectional signaling of EphAs/ephrin-As, bifunctional action of ephrins as attractants or repellents in a context-dependent manner, and complex interactions between multiple guidance molecules. In addition, spontaneous patterned neural activity has recently been shown to be required for map refinement during a brief critical period. We speculate on additional activities required for map development and suggest a synthesis of molecular and cellular mechanisms within the context of the complexities of map development.
长期以来，人们一直假定轴突导向分子的梯度控制着神经连接组织发展形成地形图。我们回顾了在确定绘图所需分子及其作用机制方面取得的进展，重点关注视觉系统，这是地图发展的主要模型。受体酪氨酸激酶的Eph家族及其配体——ephrin，仍然是唯一符合分级地形图导向分子所有标准的分子，尽管其他分子也满足一些标准。最近的报告进一步明确了它们的作用模式和新的作用，包括EphB/ephrin-B对背腹绘图的控制、EphAs/ephrin-As的双向信号传导、ephrin在上下文依赖方式下作为吸引剂或排斥剂的双功能作用，以及多种导向分子之间的复杂相互作用。此外，最近已证明在短暂的关键期内，自发的模式化神经活动是地图细化所必需的。我们推测了地图发展所需的其他活动，并在地图发展复杂性的背景下提出了分子和细胞机制的综合。
