scholarly journals Glycosylation in Axonal Guidance

2021 ◽  
Vol 22 (10) ◽  
pp. 5143
Author(s):  
Sampada P. Mutalik ◽  
Stephanie L. Gupton
Keyword(s):  
Neuronal Development ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
Axonal Pathfinding ◽  
Guidance Cues ◽  
Functional Implications ◽  
Protein Functions ◽  
Guidance Receptors ◽  
Surface Localization

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.

Transmembrane grasshopper Semaphorin I promotes axon outgrowth in vivo

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3597-3607 ◽  
Author(s):  
J.T. Wong ◽  
W.T. Yu ◽  
T.P. O'Connor
Keyword(s):  
Growth Cones ◽  
Limb Bud ◽  
Axonal Outgrowth ◽  
Axonal Pathfinding ◽  
Organ Growth ◽  
Guidance Cues ◽  
Alternative Function ◽  
Proximal Extension ◽  
Subgenual Organ

Members of the Semaphorin family of glycoproteins play an important role in axonal pathfinding by functioning as inhibitory guidance cues. Here we provide evidence that a transmembrane form of Semaphorin (Semaphorin I), which is expressed by bands of epithelial cells in the developing grasshopper limb bud, functions as an attractive/permissive cue for the growth cones of the subgenual organ. In addition, we demonstrate that Semaphorin I is needed for initial axonal outgrowth from the subgenual organ. These results are consistent with an alternative function for a transmembrane form of Semaphorin and may explain the previously reported arrest of the proximal extension of the subgenual organ growth cones in the absence of the Ti1 pioneer pathway.

FGF3 from the Hypothalamus Regulates the Guidance of Thalamocortical Axons

2020 ◽  
Vol 42 (5-6) ◽  
pp. 208-216
Author(s):  
Kuan Liu ◽  
Zhongsheng Lv ◽  
Hong Huang ◽  
Shuyang Yu ◽  
Li Xiao ◽  
...  
Keyword(s):  
Sensory Information ◽  
Axonal Pathfinding ◽  
Fibroblast Growth ◽  
High Concentration ◽  
Dependent Effect ◽  
Development Stages ◽  
Guidance Cues ◽  
Thalamocortical Axons ◽  
Ventral Diencephalon

Thalamus is an important sensory relay station: afferent sensory information, except olfactory signals, is transmitted by thalamocortical axons (TCAs) to the cerebral cortex. The pathway choice of TCAs depends on diverse diffusible or substrate-bound guidance cues in the environment. Not only classical guidance cues (ephrins, slits, semaphorins, and netrins), morphogens, which exerts patterning effects during early embryonic development, can also help axons navigate to their targets at later development stages. Here, expression analyses reveal that morphogen Fibroblast growth factor (FGF)-3 is expressed in the chick ventral diencephalon, hypothalamus, during the pathfinding of TCAs. Then, using in vitro analyses in chick explants, we identify a concentration-dependent effect of FGF3 on thalamic axons: attractant 100 ng/mL FGF3 transforms to a repellent at high concentration 500 ng/mL. Moreover, inhibition of FGF3 guidance functions indicates that FGF3 signaling is necessary for the correct navigation of thalamic axons. Together, these studies demonstrate a direct effect for the member of FGF7 subfamily, FGF3, in the axonal pathfinding of TCAs.

scholarly journals Spatiotemporal ontogeny of brain wiring

2019 ◽  
Vol 5 (6) ◽  
pp. eaav9694 ◽  
Author(s):  
A. Goulas ◽  
R. F. Betzel ◽  
C. C. Hilgetag
Keyword(s):  
Computational Modeling ◽  
Network Topology ◽  
Brain Regions ◽  
Adult Brain ◽  
Axonal Guidance ◽  
Global Network ◽  
Dependent Plasticity ◽  
Guidance Cues ◽  
And Behavior ◽  
Activity Dependent

The wiring of vertebrate and invertebrate brains provides the anatomical skeleton for cognition and behavior. Connections among brain regions are characterized by heterogeneous strength that is parsimoniously described by the wiring cost and homophily principles. Moreover, brains exhibit a characteristic global network topology, including modules and hubs. However, the mechanisms resulting in the observed interregional wiring principles and network topology of brains are unknown. Here, with the aid of computational modeling, we demonstrate that a mechanism based on heterochronous and spatially ordered neurodevelopmental gradients, without the involvement of activity-dependent plasticity or axonal guidance cues, can reconstruct a large part of the wiring principles (on average, 83%) and global network topology (on average, 80%) of diverse adult brain connectomes, including fly and human connectomes. In sum, space and time are key components of a parsimonious, plausible neurodevelopmental mechanism of brain wiring with a potential universal scope, encompassing vertebrate and invertebrate brains.

Pioneering and pathfinding by an identified neuron in the embryonic leech

Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 155-167
Author(s):  
John Y. Kuwada
Keyword(s):  
Peripheral Nerve ◽  
Large Cell ◽  
Growth Cones ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
Target Area ◽  
Guidance Cue ◽  
Identified Neuron ◽  
Peripheral Axon ◽  
Excessive Number

Numerous investigations of pathfinding by embryonic neurons, including many leech neurons, have demonstrated that pathfinding is precise. Neurons project the correct number of growth cones which grow to their target areas by making specific choices along the way. However, one leech mechanosensory neuron, the dorsal P (PD) neuron, is unusual in the sense that it initially projects an excessive number of growth cones. One of the growth cones will form the peripheral axon while the others are eliminated. This suggests that PD is one of the earliest neurons to project a peripheral axon, i.e., it may pioneer a peripheral nerve, and that it searches with its multiple growth cones for an external cue which can guide it to its target area. Examination of the early PD axon with light and electon microscopy reveals that it indeed is the first growth cone in its nerve and that it grows in contact with a large non-neuronal (DV) cell until it reaches its target area. The DV cell has a unique morphology and location: a large cell body with thin fiat processes extending from the edge of the ganglion to the target area of the PD. It is also present with its unique morphology prior to axonal outgrowth by the PD neuron. These features suggest that the DV cell may be an attractive substrate and/or axonal guidance cue for the PD peripheral axon and therefore for the entire peripheral nerve.

Axonal guidance in the chicken retina

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1443-1454 ◽  
Author(s):  
H. Stier ◽  
B. Schlosshauer
Keyword(s):  
Ganglion Cell ◽  
Radial Glia ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
Outer Retina ◽  
In Ovo ◽  
Inner Retina ◽  
Retina Development ◽  
Inhibitory Components

During retina development, ganglion cells extend their axons exclusively into the innermost tissue layer, but not into outer retina layers. In order to elucidate guiding mechanisms for axons, tissue strips of embryonic chicken retinae were explanted onto retinal cryosections (cryoculture). Ganglion cell axons originating from the explant grew preferentially on the innermost retina layer of cryosections, whereas outer tissue layers were avoided, very much as in vivo. Stereotropism, interaction with laminin of the basal lamina and axonal fasciculation did not significantly affect oriented axonal outgrowth, so that stereotropism as a guidance mechanism could be excluded. Ganglion cell axons were not directed by physical barriers, e.g. microstructured silicon oxide chips. Similarly, UV induced protein inactivation revealed that laminin present in the inner retina did not provide a guidance cue. Even in the absence of ganglion cell axons in retinal cryosections due to prior optic nerve transection in ovo, the growth preference for the innermost retina layer was maintained in cryocultures. However, oriented elongation of axons along the innermost retina layer was lost when radial glial endfeet were selectively eliminated in retinal cryosections. In addition, glial endfeet provided an excellent growth substratum when pure preparations of endfeet were employed in explant cultures. The preference for glial endfeet positioned at the inner retina surface was accompanied by the avoidance of outer retina layers, most likely because of inhibitory components in this region. This assumption is corroborated by the finding that addition of exogenous growth-promoting laminin to cryosections did not abolish the inhibition. Laminin on glass surfaces provided an excellent substratum. Axonal outgrowth was also seriously hampered on specifically purified cells of the outer retina. Most notable, however, in cryocultures aberrant innervation of outer retina layers could be induced by prior heat or protease treatment of cryosections, which pointed to proteins as potential inhibitory components. In summary the data substantiate the hypothesis that within the retina, ganglion cell axons are guided by a dual mechanism based on a permissive and an inhibitory zone. Radial glia is likely to be instructive in this process.

Axonal Guidance Signaling Pathway Is Suppressed in Human Nasal Polyps

2018 ◽  
Vol 32 (4) ◽  
pp. 208-216 ◽  
Author(s):  
Dawei Wu ◽  
Sarina K. Mueller ◽  
Angela L. Nocera ◽  
Kristen Finn ◽  
Towia A. Libermann ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Nasal Polyps ◽  
Cell Adhesion Molecule ◽  
Neuronal Cell ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
Neuronal Growth

Background Dysfunctional innervation might contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), but the state of the axonal outgrowth signaling in CRSwNP is unknown. The purpose of this study was to explore the axonal outgrowth pathway-related protein expression in CRSwNP. Methods Institutional review board approved study in which tissue proteomes were compared between control and CRSwNP patients (n = 10/group) using an aptamer-based proteomic array and confirmed by whole transcriptomic analysis. Results Compared with controls, proteins associated with axonal guidance signaling pathway such as beta-nerve growth factor, semaphorin 3A, Ras-related C3 botulinum toxin substrate 1, Bcl-2, protein kinase C delta type, and Fyn were significantly decreased in patients with CRSwNP (fold change [FC] = −1.17, P = .002; FC = −1.09, P < .001; FC = −1.33, P < .001; FC = −1.31, P < .001; FC = −1.31, P = .004; and FC = −1.20, P = 0.012, respectively). In contrast, reticulon-4 receptor, an inhibitory factor, was significantly increased in patients with CRSwNP (FC = 1.25, P < .001). Furthermore, neuronal growth-associated proteins such as ciliary neurotrophic factor receptor subunit alpha, neuronal growth regulator 1, neuronal cell adhesion molecule, neural cell adhesion molecule L1, platelet-derived growth factor subunit A, and netrin-4 were all significantly decreased in patients with CRSwNP (FC = −1.25, P < .001; FC = −1.27, P = .002; FC = −1.65, P = .013; FC = −4.20, P < .001; FC = −1.28, P < .001; and FC = −2.31, P < .001, respectively). In contrast, tissue eosinophil count ( P < .001) and allergic inflammation factors such as IgE, periostin, and galectin-10 were all significantly increased in patients with CRSwNP (FC = 12.28, P < .001; FC = 3.95, P < .001; and FC = 2.44, P < .001, respectively). Furthermore, the log FC of the studied proteins expression significantly and positively correlated with log FC of their mRNA expression ( P < .001, r = .88). Conclusions Axonal guidance signaling and neural growth factors pathways proteins are significantly suppressed in eosinophilic CRSwNP.

scholarly journals Cell behaviors regulated by guidance cues in collective migration of border cells

2011 ◽  
Vol 192 (3) ◽  
pp. 513-524 ◽  
Author(s):  
Minna Poukkula ◽  
Adam Cliffe ◽  
Rishita Changede ◽  
Pernille Rørth
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Cell Group ◽  
Border Cells ◽  
Collective Migration ◽  
Cell Behaviors ◽  
Guidance Cues ◽  
Guidance Receptors ◽  
Endothelial Growth Factor

Border cells perform a collective, invasive, and directed migration during Drosophila melanogaster oogenesis. Two receptor tyrosine kinases (RTKs), the platelet-derived growth factor/vascular endothelial growth factor–related receptor (PVR) and the epidermal growth factor receptor (EGFR), are important for reading guidance cues, but how these cues steer migration is not well understood. During collective migration, front, back, and side extensions dynamically project from individual cells within the group. We find that guidance input from both RTKs affects the presence and size of these extensions, primarily by favoring the persistence of front extensions. Guidance cues also control the productivity of extensions, specifically rendering back extensions nonproductive. Early and late phases of border cell migration differ in efficiency of forward cluster movement, although motility of individual cells appears constant. This is caused by differences in behavioral effects of the RTKs: PVR dominantly induces large persistent front extensions and efficient streamlined group movement, whereas EGFR does not. Thus, guidance receptors steer movement of this cell group by differentially affecting multiple migration-related features.

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