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.

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.

scholarly journals A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion

2016 ◽  
Vol 213 (2) ◽  
pp. 261-274 ◽  
Author(s):  
Russell E. McConnell ◽  
J. Edward van Veen ◽  
Marina Vidaki ◽  
Adam V. Kwiatkowski ◽  
Aaron S. Meyer ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Actin Polymerization ◽  
Growth Cones ◽  
Guidance Cues ◽  
Guidance Cue ◽  
3D Environments ◽  
Direct Binding ◽  
Mouse Dorsal Root Ganglion ◽  
Axon Repulsion

Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor.

scholarly journals RNA-based mechanisms underlying axon guidance

2013 ◽  
Vol 202 (7) ◽  
pp. 991-999 ◽  
Author(s):  
Toshiaki Shigeoka ◽  
Bo Lu ◽  
Christine E. Holt
Keyword(s):  
Axon Guidance ◽  
Translational Control ◽  
Growth Cones ◽  
Receptor Activation ◽  
Neural Pathways ◽  
Neuronal Circuitry ◽  
Guidance Cues ◽  
Spatiotemporal Control

Axon guidance plays a key role in establishing neuronal circuitry. The motile tips of growing axons, the growth cones, navigate by responding directionally to guidance cues that pattern the embryonic neural pathways via receptor-mediated signaling. Evidence in vitro in the last decade supports the notion that RNA-based mechanisms contribute to cue-directed steering during axon guidance. Different cues trigger translation of distinct subsets of mRNAs and localized translation provides precise spatiotemporal control over the growth cone proteome in response to localized receptor activation. Recent evidence has now demonstrated a role for localized translational control in axon guidance decisions in vivo.

scholarly journals Gradients and Growth Cone Guidance of Grasshopper Neurons

2003 ◽  
Vol 51 (4) ◽  
pp. 445-454 ◽  
Author(s):  
Arthur T. Legg ◽  
Timothy P. O'Connor
Keyword(s):  
Nervous System ◽  
Long Range ◽  
Growth Cone ◽  
Growth Cones ◽  
Path Finding ◽  
Guidance Cues ◽  
Cone Function ◽  
The Absolute ◽  
Growth Cone Guidance

The generation of a functional nervous system is dependent on precise path-finding of axons during development. This pathfinding is directed by the distribution of local and long-range guidance cues, the latter of which are believed to be distributed in gradients. Gradients of guidance cues have been associated with growth cone function for over a hundred years. However, little is known about the mechanisms used by growth cones to respond to these gradients, in part owing to the lack of identifiable gradients in vivo. In the developing grasshopper limb, two gradients of the semaphorin Sema-2a are necessary for correct neuronal pathfinding in vivo. The gradients are found in regions where growth cones make critical steering decisions. Observations of different growth cone behaviors associated with these gradients have provided some insights into how growth cones respond to them. Growth cones appear to respond more faithfully to changes in concentration, rather than absolute levels, of Sema-2a expression, whereas the absolute levels may regulate growth cone size.

scholarly journals Coupling of dynamic microtubules to F-actin by Fmn2 regulates chemotaxis of neuronal growth cones

2021 ◽  
Author(s):  
Tanushree Kundu ◽  
Priyanka Dutta ◽  
Dhriti Nagar ◽  
Sankar Maiti ◽  
Aurnab Ghose
Keyword(s):  
Single Molecule ◽  
Actin Filaments ◽  
Growth Cones ◽  
Axonal Pathfinding ◽  
Spinal Neurons ◽  
Critical Function ◽  
Superresolution Imaging ◽  
Cellular Processes ◽  
Neuronal Growth Cones

Dynamic co-regulation of the actin and microtubule subsystems enables the highly precise and adaptive remodelling of the cytoskeleton necessary for critical cellular processes, like axonal pathfinding. The modes and mediators of this interpolymer crosstalk, however, are inadequately understood. We identify Fmn2, a non-diaphanous related formin associated with cognitive disabilities, as a novel regulator of cooperative actin-microtubule remodelling in growth cones. We show that Fmn2 stabilizes microtubules in the growth cones of cultured spinal neurons and also in vivo. Superresolution imaging revealed that Fmn2 facilitates guidance of exploratory microtubules along actin bundles into the chemosensory filopodia. Using live imaging, biochemistry and single-molecule assays we show that a C-terminal domain in Fmn2 is necessary for the dynamic association between microtubules and actin filaments. In the absence of the cross- bridging function of Fmn2, filopodial capture of microtubules is compromised resulting in de-stabilized filopodial protrusions and deficits in growth cone chemotaxis. Our results uncover a critical function for Fmn2 in actin-microtubule crosstalk in neurons and demonstrate that modulating microtubule dynamics via associations with F-actin is central to directional motility.

scholarly journals Robo and Ror function in a common receptor complex to regulate Wnt-mediated neurite outgrowth in Caenorhabditis elegans

2018 ◽  
Vol 115 (10) ◽  
pp. E2254-E2263 ◽  
Author(s):  
Jiaming Wang ◽  
Mei Ding
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Cones ◽  
Asymmetric Distribution ◽  
Receptor Complex ◽  
Biological Processes ◽  
Membrane Recruitment ◽  
Guidance Cues ◽  
Downstream Effector ◽  
Common Receptor

Growing axons are exposed to various guidance cues en route to their targets, but the mechanisms that govern the response of growth cones to combinations of signals remain largely elusive. Here, we found that the sole Robo receptor, SAX-3, in Caenorhabditis elegans functions as a coreceptor for Wnt/CWN-2 molecules. SAX-3 binds to Wnt/CWN-2 and facilitates the membrane recruitment of CWN-2. SAX-3 forms a complex with the Ror/CAM-1 receptor and its downstream effector Dsh/DSH-1, promoting signal transduction from Wnt to Dsh. sax-3 functions in Wnt-responsive cells and the SAX-3 receptor is restricted to the side of the cell from which the neurite is extended. DSH-1 has a similar asymmetric distribution, which is disrupted by sax-3 mutation. Taking these results together, we propose that Robo receptor can function as a Wnt coreceptor to regulate Wnt-mediated biological processes in vivo.

Disruption of pioneer growth cone guidance in vivo by removal of glycosyl-phosphatidylinositol-anchored cell surface proteins

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 507-519 ◽  
Author(s):  
W.S. Chang ◽  
K. Serikawa ◽  
K. Allen ◽  
D. Bentley
Keyword(s):  
Cell Surface ◽  
Growth Cone ◽  
Growth Cones ◽  
Surface Proteins ◽  
Limb Bud ◽  
Cell Surface Proteins ◽  
Glycosyl Phosphatidylinositol ◽  
Stage Of Development ◽  
Growth Cone Guidance

Cell surface proteins anchored to membranes via covalently attached glycosyl-phosphatidylinositol (GPI) have been implicated in neuronal adhesion, promotion of neurite outgrowth and directed cell migration. Treatment of grasshopper embryos with bacterial phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme that cleaves the GPI anchor, often induced disruptions in the highly stereotyped migrations of peripheral pioneer growth cones and afferent neuron cell bodies. In distal limb regions of embryos treated with PI-PLC at early stages of pioneer axon outgrowth, growth cones lost their proximal orientation toward the central nervous system (CNS) and turned distally. Pioneer growth cones in treated limbs also failed to make a characteristic ventral turn along the trochanter-coxa (Tr-Cx) segment boundary, and instead continued to grow proximally across the boundary. Treatment at an earlier stage of development caused pre-axonogenesis Cx1 neurons to abandon their normal circumferential migration and reorient toward the CNS. None of these abnormal phenotypes were observed in limbs of untreated embryos or embryos exposed to other phospholipases that do not release GPI-anchored proteins. Incubation of embryos with PI-PLC effectively removed immunoreactivity for fasciclin I, a GPI-anchored protein expressed on a subset of neuronal surfaces. These results suggest that cell surface GPI-anchored proteins are involved in pioneer growth cone guidance and in pre-axonogenesis migration of neurons in the grasshopper limb bud in vivo.

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 Drosophila Growth Cones Advance by Forward Translocation of the Neuronal Cytoskeletal Meshwork In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80136 ◽  
Author(s):  
Douglas H. Roossien ◽  
Phillip Lamoureux ◽  
David Van Vactor ◽  
Kyle E. Miller
Keyword(s):  
Growth Cones

scholarly journals Experimental studies on the differentiation of embryonic tissues growing in vivo and in vitro .—II. The development of the isolated early embryonic eye of the fowl when cultivated in vitro

1926 ◽  
Vol 100 (703) ◽  
pp. 273-283 ◽  
Keyword(s):  
Medical Research ◽  
Research Council ◽  
Medical Research Council ◽  
Experimental Studies ◽  
Limb Bud ◽  
Progressive Development ◽  
Embryonic Tissues ◽  
Self Differentiation

In a previous communication (Strangeways and Fell, 1926) it was shown that if the undifferentiated limb-bud of the embryonic Fowl was cultivated in vitro , it underwent a considerable amount of progressive development. This capacity for independent development in vitro possessed by an isolated organ has been further investigated, and for these later experiments the writers have employed the early embryonic eye, a structure endowed with more complex potentialities than the limb-bud. As a result of these experiments it was found that the eyes of young Fowl embryos possess, in a remarkable degree, the faculty for self-differentiation in vitro and for “organotypic” growth as defined by Maximow (1925). The previous work on organotypic growth in vitro has already been briefly outlined in the writers’ earlier paper and need not be discussed here. The expenses connected with the experiments described in this communication were met by the Medical Research Council, to whom the writers desire to express their thanks.

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