SPECIFICITY OF SYNAPSE FORMATION

发育神经生物学中一个尚未解决的主要问题是如何生长 轴突向它们的目标区域导航。这项建议是针对 确定引导体内轴突生长的机制。的决定 这些机制将提供必要的信息，以便继续 轴突形成的细胞、分子和遗传学基础研究 指导，以及对神经可能的机制的洞察 再生。 这只雏鸟的交感神经系统被证明是非常 对活体轴突引导研究很有用。它的解剖结构相对来说 简单，发展很好理解，和假定的途径 生长中的轴突是可以预测的。这个实验室之前的研究已经 交感节前投射是节段性的， 从一开始就正确，与目标组织无关。更近的 结果表明，节前轴突的时空分布 突起可以受到周围体细胞中胚层的影响。已被占用 综上所述，这些发现表明神经元/神经的某些特性 管或邻近的体细胞中胚层可以影响特异性。 节前投射。 为了确定哪些机制参与指导 感同身受的节前轴突，我提出了四个独立的模型。 每个模型都只测试一种对交感神经的潜在影响。 节前生长，模型并不是相互排斥的。这个 模型基于以下潜在影响：L)内在影响 体细胞中胚层的同一性；2)体细胞的成熟 中胚层；3)节前神经元/神经元的内在同一性 4)与邻近节前神经元的相互作用。 因为我在实验操作中获得了专业知识 对于鸡胚胎，有可能在体内测试这些模型中的每一个。 实验技术主要涉及异时性和/或 异位神经管或体节移植，随后进行评估 节前投射的变化。这项技术已经产生了一些 过去取得了非常丰硕的成果。对于每个模型，需要进行多次实验 都是为了增加结果的可靠性而提出的。这个 实验被设计成只改变一个变量，使得正值 结果只有一种解释--模型是 支持。初步研究已经提供了证据支持一些 建议的模型中。

A major unresolved issue in developmental neurobiology is how growing axons navigate toward their target areas. This proposal is directed to identify the mechanisms that guide growing axons in vivo. Determination of these mechanisms will provide the necessary information for continued research into the cellular, molecular, and genetic bases for axonal guidance, as well as insight into possible mechanisms for nerve regeneration. The sympathetic nervous system of the chick has proven to be extremely useful for axonal guidance studies in vivo. Its anatomy is relatively simple, the development well understood, and the presumptive pathways of growing axons are predictable. Previous studies from this laboratory have shown that sympathetic preganglionic projections are segment specific, correct from the outset, and independent of the target tissue. More recent results have shown that the spatiotemporal pattern of preganglionic axon outgrowth can be influenced by the surrounding somitic mesoderm. Taken together, these findings suggest that some properties of the neuron/neural tube, or the adjacent somitic mesoderm, can influence the specificity of preganglionic projections. In order to determine which mechanisms are involved in the guidance of sympathetic preganglionic axons, I have proposed four independent models. Each model is designed to test only one potential influence on sympathetic preganglionic outgrowth, and the models are not mutually exclusive. The models are based on the following potential influences: l) the intrinsic identity of the somitic mesoderm; 2) the maturation of the somitic mesoderm; 3) the intrinsic identity of the preganglionic neurons/neural tube segments; and 4) interactions with neighboring preganglionic neurons. Because of the expertise that I have gained in experimental manipulations of the chick embryo, it is possible to test each of these models in vivo. The experimental technique involves mainly heterochronic and/or heterotopic neural tube or somite transplantations, followed by evaluation of changes in preganglionic projections. This technique has yielded some very fruitful results in the past. For each model, multiple experiments are proposed in order to increase the reliability of the results. The experiments are designed to alter only one variable, such that positive results lend themselves to only one interpretation--that the model is supported. Preliminary studies have provided evidence in support of some of the proposed models.