Regulation of axonal branching in vivo

我们的神经系统由多达1万亿个神经元组成，这些神经元控制着思维、感觉、运动、学习和记忆等活动。这是可能的，因为神经元是高度互联的（形成神经元回路），并以一种受调节的方式连接到身体的所有器官。了解神经元回路如何建立和修复是发育和再生神经生物学的主要挑战。此外，在受伤后，神经回路往往不能重建，导致严重的残疾。这在脊髓损伤后尤其重要，脊髓损伤可导致部分或完全瘫痪。在我的实验室，我们正在研究在整个生物体的复杂环境中调节神经元生长和形状（或形态）的分子机制。特别是，我们正在研究运动神经元的发育和功能。运动神经元是高度特化的细胞，有长长的延伸，被称为轴突，它可以从细胞体延伸到一米远的地方，到达并支配它们的目标器官——肌肉。因此，必须严格控制这些轴突的生长、引导和形态。我们使用爪蟾蛙作为实验模型，因为胚胎在外部发育，使我们能够直接看到导致运动神经元发育的事件。此外，青蛙蝌蚪在受精后2-3天开始游泳。因此，我们可以将运动神经元发育中的缺陷与它们的功能测试联系起来。我们最近发现了一个在运动神经元中特异性表达的分子，它在轴突生长和分支中起着重要作用。我们希望在这一最新发现的基础上，深入了解这群神经元中轴突分支的调节。为此，我们将结合最先进的活胚胎实验和培养神经细胞研究来揭示轴突分支过程中发生的分子和细胞事件。虽然我们知道这些分子在物种间是保守的，但我们的最终目标是研究调节轴突分支的机制是否也适用于人类运动神经元。这将使我们能够为脊髓损伤等疾病探索新的治疗途径。

Our nervous system is made of up to 1000 billion neurons governing thinking, feeling, moving, learning and memory amongst other activities. This is possible because neurons are highly interconnected (creating neuronal circuits) and connected to all the organs of the body in a regulated manner. Understanding how neuronal circuits are established and repaired is a major challenge of developmental and regenerative neurobiology. Furthermore, upon injury, neuronal circuits often fail to reform, leading to severe disabilities. This is particularly important after spinal cord injuries which can lead to partial or total paralysis. In my laboratory, we are studying the molecular mechanisms regulating neuronal growth and shape (or morphology) in the complex environment of the whole organism. In particular, we are investigating how motor neurons develop and function. Motor neurons are highly specialised cells with long extensions, called axons, which can travel up to one metre away from their cell body to reach and innervate their target organs, the muscles. Therefore, the growth, guidance and morphology of these axons must be tightly controlled. We use the frog Xenopus as an experimental model because the embryos develop externally allowing us to visualise directly the events leading to motor neurons development. Furthermore, frog tadpoles start to swim 2-3 days after fertilisation. We can therefore correlate defects in motor neurons development with functional tests on their function. We have recently identified a molecule expressed specifically in motor neurons which has an essential role in axonal growth and branching. We want to build on this recent discovery to gain insight in the regulation of axonal branching in this population of neurons. To this end, we will combine state-of-the-art experiments in living embryos and studies in neuronal cells in culture to uncover the molecular and cellular events that occur during axonal branching. Whilst we know that the molecules are conserved across species, our ultimate goal is to investigate whether the mechanism regulating axonal branching is also applicable in human motor neurons. This will allow us to explore new therapeutic avenues for conditions such as spinal cord injuries.