神经系统双侧回路的发育:从分子机制到小脑及其在神经发育障碍中的意义

J. A. Moreno Bravo
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引用次数: 0

摘要

大脑是我们拥有的最复杂的器官,是它定义了我们是人类。它是智力、思想和记忆的基础。此外,它通过感官解读世界,发起运动并控制我们的行为。这个器官的正确功能是建立在数以百万计的神经元之间正确的连接模式的基础上的,这使得它们之间能够进行精确和有效的交流。这些神经网络在胚胎和出生后发育期间出现。适当的神经回路的形成依赖于由特定分子机制控制的各种非常精确的精心安排的事件。因此,这些早期事件的失败将导致脑部病变和复杂的疾病。在过去的几十年里,在识别和理解指导轴突和神经回路发育的分子的作用机制方面取得了显著的进展。然而,它们在体内神经回路形成的许多方面的作用仍然很大程度上未知,特别是这种初始连接的损伤是如何在复杂的神经发育病理中产生的。在这里,我重点介绍了我的部分贡献和最近的进展,这些贡献和进展揭示了调节轴突引导和中枢神经系统双侧回路布线的机制的复杂性。此外,我还讨论了如何理解小脑双侧回路的发展对于理解各种神经发育病理学的出现至关重要。
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Development of bilateral circuits of the nervous system: From molecular mechanisms to the cerebellum and its implication in neurodevelopmental disorders
The brain is the most complex organ we have, and it is the one that defines us as human beings. It is the basis of intelligence, of our thoughts and memories. In addition, it interprets the world through the senses, initiates movement and controls our behaviors. The correct functioning of this organ is based on the correct establishment of connectivity patterns between the millions of neurons which enable a precise and efficient communication between them. These neural networks emerge during embryonic and postnatal development. The formation of proper neuronal circuitry relies on diverse and very precisely orchestrated events controlled by specific molecular mechanisms. Therefore, failures in these early events will lead to brain pathologies and complex disorders. In the last decades, remarkable progress has been made in identifying and in understanding the mechanisms of action of the molecular that direct axon and neural circuitry development. However, their role in vivo in many aspects of neural circuit formation remains largely unknown, particularly how the impairment of this initial connectivity derives in complex neurodevelopmental pathologies. Here, I highlight part of my contributions and recent advances that shed light on the complexity of mechanisms that regulate axon guidance and the wiring of the bilateral circuits of the central nervous system. Furthermore, I discuss about how understanding the development of bilateral circuits of the cerebellum is essential to understand the emergence of diverse neurodevelopmental pathologies.
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