A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways

Ye, Xiyue; Qiu, Yan; Gao, Yuqing; Wan, Dong; Zhu, Huaqing

doi:10.1155/2019/1719829

Cited by 31 publications

(102 citation statements)

References 281 publications

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“…It may inhibit the axon growth by stimulating neurons to induce RhoA and ROCK (Rho-associated coiled-coil protein kinase) expression [ 5 ]. It has been confirmed that RGMa may cause cone collapse by activating downstream Rho-GTPase activity [ 26 ]. In addition, RGMa can regulate the phosphorylation of collapse response mediator protein-2 (CRMP-2) by activating Rho-kinase and glycogen synthase kinase 3 β (GSK-3 β ) signaling pathways, thus regulating the axonal shortening [ 26 ].…”

Section: Role Of Rgma In Cns Pathologymentioning

confidence: 99%

“…It has been confirmed that RGMa may cause cone collapse by activating downstream Rho-GTPase activity [ 26 ]. In addition, RGMa can regulate the phosphorylation of collapse response mediator protein-2 (CRMP-2) by activating Rho-kinase and glycogen synthase kinase 3 β (GSK-3 β ) signaling pathways, thus regulating the axonal shortening [ 26 ]. Two independent c-RGMa and n-RGMa can activate different intracellular pathways to regulate neuronal survival: (1) in general, c-RGMa combines with Neogenin to activate RhoA through Unc5 and LARG ( Figure 1(b) ) [ 27 – 29 ].…”

Section: Role Of Rgma In Cns Pathologymentioning

confidence: 99%

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Repulsive Guidance Molecule-a and Central Nervous System Diseases

Tang

Zeng

et al. 2021

BioMed Research International

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Repulsive guidance molecule-a (RGMa) is a member of glycosylphosphatidylinositol- (GPI-) anchored protein family, which has axon guidance function and is widely involved in the development and pathological processes of the central nervous system (CNS). On the one hand, the binding of RGMa and its receptor Neogenin can regulate axonal guidance, differentiation of neural stem cells into neurons, and the survival of these cells; on the other hand, RGMa can inhibit functional recovery of CNS by inhibiting axonal growth. A number of studies have shown that RGMa may be involved in the pathogenesis of CNS diseases, such as multiple sclerosis, neuromyelitis optica spectrum diseases, cerebral infarction, spinal cord injury, Parkinson’s disease, and epilepsy. Targeting RGMa can enhance the functional recovery of CNS, so it may become a promising target for the treatment of CNS diseases. This article will comprehensively review the research progression of RGMa in various CNS diseases up to date.

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Section: Role Of Rgma In Cns Pathologymentioning

confidence: 99%

Section: Role Of Rgma In Cns Pathologymentioning

confidence: 99%

Repulsive Guidance Molecule-a and Central Nervous System Diseases

Tang

Zeng

et al. 2021

BioMed Research International

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“…Despite the identification of novel guidance cues and mechanisms, how a limited number of cues generate the complex diversity of axonal trajectories remains a fascinating puzzle. The current understanding of the cellular and developmental regulation of axonal guidance pathways has been discussed extensively in recent reviews [ 4 , 7 , 13 , 14 , 15 ]. Beyond these mechanisms, posttranslational modifications contribute significantly to regulating axon guidance pathways [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Glycosylation in Axonal Guidance

Mutalik

Gupton

2021

IJMS

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How millions of axons navigate accurately toward synaptic targets during development is a long-standing question. Over decades, multiple studies have enriched our understanding of axonal pathfinding with discoveries of guidance molecules and morphogens, their receptors, and downstream signalling mechanisms. Interestingly, classification of attractive and repulsive cues can be fluid, as single guidance cues can act as both. Similarly, guidance cues can be secreted, chemotactic cues or anchored, adhesive cues. How a limited set of guidance cues generate the diversity of axonal guidance responses is not completely understood. Differential expression and surface localization of receptors, as well as crosstalk and spatiotemporal patterning of guidance cues, are extensively studied mechanisms that diversify axon guidance pathways. Posttranslational modification is a common, yet understudied mechanism of diversifying protein functions. Many proteins in axonal guidance pathways are glycoproteins and how glycosylation modulates their function to regulate axonal motility and guidance is an emerging field. In this review, we discuss major classes of glycosylation and their functions in axonal pathfinding. The glycosylation of guidance cues and guidance receptors and their functional implications in axonal outgrowth and pathfinding are discussed. New insights into current challenges and future perspectives of glycosylation pathways in neuronal development are discussed.

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“…In this review, we focus on guidance cue/ receptor families that are critical to form major tracts in the cerebral cortex, cerebellum, and hippocampus: Semaphorin/Neuropilin, Netrin/DCC, and Slit/Robo. 3 We highlight tracts in each region-the CC in the cerebral cortex, climbing and mossy fibers in the cerebellum, and mossy fibers in the hippocampus. We aim to explore FASD pathology potentially associated with axon guidance in these regions.…”

Section: Introductionmentioning

confidence: 99%

White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance

Mathews

Dewees

Diaz

et al. 2021

Exp Biol Med (Maywood)

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Fetal Alcohol Spectrum Disorders (FASDs) describe a range of deficits, affecting physical, mental, cognitive, and behavioral function, arising from prenatal alcohol exposure. FASD causes widespread white matter abnormalities, with significant alterations of tracts in the cerebral cortex, cerebellum, and hippocampus. These brain regions present with white-matter volume reductions, particularly at the midline. Neural pathways herein are guided primarily by three guidance cue families: Semaphorin/Neuropilin, Netrin/DCC, and Slit/Robo. These guidance cue/receptor pairs attract and repulse axons and ensure that they reach the proper target to make functional connections. In several cases, these signals cooperate with each other and/or additional molecular partners. Effects of alcohol on guidance cue mechanisms and their associated effectors include inhibition of growth cone response to repellant cues as well as changes in gene expression. Relevant to the corpus callosum, specifically, developmental alcohol exposure alters GABAergic and glutamatergic cell populations and glial cells that serve as guidepost cells for callosal axons. In many cases, deficits seen in FASD mirror aberrancies in guidance cue/receptor signaling. We present evidence for the need for further study on how prenatal alcohol exposure affects the formation of neural connections which may underlie disrupted functional connectivity in FASD.

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A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways

Cited by 31 publications

References 281 publications

Repulsive Guidance Molecule-a and Central Nervous System Diseases

Repulsive Guidance Molecule-a and Central Nervous System Diseases

Glycosylation in Axonal Guidance

White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance

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