生长锥诱向中Eph-ephrins导向分子家族的信号转导

轴突导向(axon guidance)是神经细胞发育的一种特殊的运动形式,通过其末端膨大的结构-生长锥(growth cone)表面的受体识别生长路径上不同时间和空间表达的信号分子,寻找到靶标后获得停止前进的信号,使轴突与靶细胞建立突触联系[1]。生长锥诱向(turning)调节轴突延伸,是轴突导向     

轴突生长诱向因子(Netrin)基因家族研究进展

<正> 在神经系统发育过程中,神经与其靶细胞之间精确联系的形成是依靠多种细胞外诱向因子介导实现的。这些因子通过作用于轴突生长锥上的相应受体而诱导或排斥轴突生长,从而决定了轴突的生长路线以及轴突与特定靶细胞的功能联系。Netrin基因家族是此类因子的代表之一,根据位于轴突生长锥上的Netrin受体不同,Netrin在神经发育的不同时     

神经系统轴突生长的数值模拟

目的数值模拟神经系统在发育过程中轴突的生长情况。方法根据神经发育原理,建立具有一定刚性的非线性混合抛物型偏微分方程组,运用ADI差分格式和改进的欧拉法作数值分析。结果 (1)在一个正方形平面区域内有10个轴突以相等的间距围成圆形,当中心有1个靶细胞时,轴突生长路径的数值模拟结果与前人所做的有关结果一致;(2)轴突的初始位置同(1),当中央有4个两两上下并排分布的靶细胞时,数值模拟结果很好地反映了轴突生长时的趋化性;(3)在区域的近上、下边界分别有一串靶细胞和一串轴突时,数值模拟结果较好地反映了轴突结集生长时的成束和解束现象。结论本文给出的数学模型和数值主法能够较好地模拟有关实验所观测到的主要现象。     

轴突生长导向因子Sema 3A在鸡胚脊髓中的表达

为了探讨轴突生长导向因子 Sema 3 A在鸡胚脊髓中的表达 ,扩增含有 Sema 3 A编码序列的质粒并制备 RNA探针 ,应用原位杂交技术检测 Sema3 A m RNA在鸡胚不同发育期 ( E4、E6、E7、E8)脊髓中的表达。结果表明 ,在鸡胚发育的第 4d( E4) ,Sema 3 A m RNA表达在神经管周围和脊髓 ;在 E6期和 E7期 ,Sema 3 A表达在中央管周围和脊髓前角 ,以腹侧为著 ;在 E8期 ,表达主要集中在前角运动神经元 ,其它部位则信号明显较弱。结论 :Sema3 A在鸡胚不同发育期脊髓中的表达是动态的 ,呈现向腹侧集中的趋势 ;它可能在脊髓发育期轴突的投射中起着导向作用     

胃癌发病的分子机理研究

本就近年来胃癌的分子机理研究，包括染色体染合性丢失，抑癌基因的丢失与失活，癌基因的扩增，转移相关基因的异常表达和遗传的不稳定性等作一综述，对阐明胃癌的发生发展机制具有重要意义。     

淋巴细胞归巢至肠粘膜组织的分子机理

淋巴细胞不断地从毛细血管后微静脉迁移至组织 ,然后通过淋巴循环再回流至血液 ,这个过程称为淋巴细胞再循环 (Ｌｙｍｐｈｏｃｙｔｅｒｅｃｉｒｃｕｌａｔｉｏｎ)。淋巴细胞在机体内巡游可以发现外源性抗原和细菌 ,并参与炎症反应 ,起重要的免疫监视作用[1] 。淋巴细胞从血液迁     

脑梗塞引起神经元凋亡的分子生化机理

脑 梗塞引起的局限性脑缺血 ,是老年人群中常见的意外事件。这种突发性的意外事件有的是持久性的 ,由于脑局部持续性缺氧和缺营养 ,立即引起神经元的原发性死亡 ,导致相应的对侧性瘫痪 ,这种情况是难于实现治疗的。但更多的是可逆性的 ,即形成再灌注 (ｒｅｐｅｒｆｕｓｉｏｎ)而引起迟发的继发性神经元死亡 (ｄｅｌａｙｅｄｓｅｃｏｎｄａｒｙｄｅａｔｈｏｆｎｅｕ ｒｏｎｓ,ＤＳＤＮ) ,这种情况是可以采取一定的防御和延缓措施的。因此 ,近年来对于神经元的凋亡和抗凋亡机理以及对ＤＳＤＮ的防护研究[1 ] ,引起医学界的高度关注。1　细胞凋…     

调控P53蛋白功能的分子机理

Ｐ５３是一种抑癌基因，其编码产物野生型Ｐ５３蛋白在维持细胞正常生长及抑制生增殖过程中起重要作用，Ｐ５３蛋白功能的丧失和多种肿瘤有关。参与调控Ｐ５３蛋白功能的因素很多，本着重从基因组水平、转录后水平、翻译后调节及Ｐ５３蛋白和其它基因产物的相互作用等几个方面加以综述，以期进一步揭示调控Ｐ５３蛋白功能的分子机制。     

Molecular mechanisms of axon guidance in the developing corticospinal tract

The great repertoire of movements in higher order mammals comes courtesy of the corticospinal tract (CST) which is able to initiate precise movement of the entire musculature of the axial and limb muscle groups. It forms the longest axonal trajectory in the mammalian central nervous system and its axons must navigate the entire length of the central nervous system--from its origins in the deeper layers of the cerebral cortex down through the cerebral peduncles and brainstem and along the entire length of the spinal cord. This period of navigation is incredibly complex, and relies upon the coordinated regulation of a collection of molecular guidance cues - coming from all of the known major families of guidance cues - the ephrins, slits, Netrins and Semaphorins - that work together to steer the growing axonal tips through the brain and spinal cord. As such a long tract, the CST forms an excellent experimental model to investigate the nature of molecular cues that sequentially guide axons through the central nervous system. Using the rodent as a model system, this review discusses each step of axonal guidance through the major brain regions--starting from the decision to grow ventrally out of the cortical plate to the eventual activity-dependent refinement of circuitry in the spinal grey matter. In recent years, the identification of these guidance cues and their proposed mode of action is beginning to give us a picture at a molecular level of how the CST is guided so accurately over such a long distance.     

Tissue-engineered platforms of axon guidance

Tissue engineering provides a valuable tool for in vitro investigation of complex in vivo environments. A particular application of tissue-engineered in vitro platforms in neuroscience and regenerative medicine is the fabrication of controlled microenvironments for the study of axon guidance, with the goal of informing strategies to overcome nerve injury. The innovative design of tissue-engineered scaffolds that incorporate multiple guidance cues and cell types into various environments is advancing the understanding of how neurons integrate guidance information to make growth decisions. This review focuses on recent strategies that present neurons with multiple cues with micro- and nanoscale resolution in order to study the interactions between neurons and their local environment during axon guidance.     

Permeable guidance channels containing microfilament scaffolds enhance axon growth and maturation

Successful peripheral nerve regeneration is still limited in artificial conduits, especially for long lesion gaps. In this study, porous poly(L-lactide-co-DL-lactide, 75:25) (PLA) conduits were manufactured with 16 poly(L-lactide) (PLLA) microfilaments aligned inside the lumen. Fourteen and 18 mm lesion gaps were created in a rat sciatic nerve lesion model. To evaluate the combined effect of permeable PLA conduits and microfilament bundles on axon growth, four types of implants were tested for each lesion gap: PLA conduits with 16 filaments; PLA conduits without filaments; silicone conduits with 16 filaments; and silicone conduits without filaments. Ten weeks following implantation, regeneration within the distal nerve was compared between corresponding groups. Antibodies against the markers S100, calcitonin gene related peptide (CGRP), RMDO95, and P0 were used to identify Schwann cells, unmyelinated axons, myelinated axons, and myelin, respectively. Results demonstrated that the filament scaffold enhanced tissue cable formation and Schwann cell migration in all groups. The filament scaffold enhanced axonal regeneration toward the distal stump, especially across long lesion gaps, but significance was only achieved with PLA conduits. When compared to corresponding silicone conduits, permeable PLA conduits enhanced myelinated axon regeneration across both lesion gaps and achieved significance only in combination with filament scaffolds. Myelin staining indicated PLA conduits supported axon myelination with better myelin quantity and quality when compared to silicone conduits.     

EGCG stabilizes growth cone filopodia and impairs retinal ganglion cell axon guidance

Background : Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain. Results : EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid‐diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior. Conclusions : We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667–677, 2016. © 2016 Wiley Periodicals, Inc.     

Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration

Recognition molecules of the immunoglobulin superfamily have important roles in neuronal interactions during ontogeny, including migration, survival, axon guidance and synaptic targeting. Their downstream signal transduction events specify whether a cell changes its place of residence or projects axons and dendrites to targets in the brain, allowing the construction of a dynamic neural network. A wealth of recent discoveries shows that cell adhesion molecules interact with attractant and repellent guidance receptors to control growth cone and cell motility in a coordinate fashion. We focus on the best-studied subclasses, the neural cell adhesion molecule NCAM and the L1 family of adhesion molecules, which share important structural and functional features. We have chosen these paradigmatic molecules and their interactions with other recognition molecules as instructive for elucidating the mechanisms by which other recognition molecules may guide cell interactions during development or modify their function as a result of injury, learning and memory.     

Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone

Asymmetric elevation of the Ca(2+) concentration in the growth cone can mediate both attractive and repulsive axon guidance. Ca(2+) signals that are accompanied by Ca(2+)-induced Ca(2+) release (CICR) trigger attraction, whereas Ca(2+) signals that are not accompanied by CICR trigger repulsion. The molecular machinery downstream of Ca(2+) signals, however, remains largely unknown. Here we report that asymmetric membrane trafficking mediates growth cone attraction. Local photolysis of caged Ca(2+), together with CICR, on one side of the growth cone of a chick dorsal root ganglion neuron facilitated the microtubule-dependent centrifugal transport of vesicles towards the leading edge and their subsequent vesicle-associated membrane-protein 2 (VAMP2)-mediated exocytosis on the side with an elevated Ca(2+) concentration. In contrast, Ca(2+) signals without CICR had no effect on the vesicle transport. Furthermore, pharmacological inhibition of VAMP2-mediated exocytosis prevented growth cone attraction, but not repulsion. These results strongly suggest that growth cone attraction and repulsion are driven by distinct mechanisms, rather than using the same molecular machinery with opposing polarities.     

Midline axon guidance and human genetic disorders

In bilaterally symmetric animals, many axons cross the midline to interconnect the left and right sides of the central nervous system (CNS). This process is critical for the establishment of neural circuits that control the proper integration of information perceived by the organism and the resulting response. While neurons at different levels of the CNS project axons across the midline, the molecules that regulate this process are common to many if not all midline-crossing regions. This article reviews the molecules that function as guidance cues at the midline in the developing vertebrate spinal cord, cortico-spinal tract and corpus callosum. As well, we describe the mutations that have been identified in humans that are linked to axon guidance and midline-crossing defects.