scholarly journals Axon guidance cue Netrin-1 has dual function in angiogenesis

2007 ◽  
Vol 6 (5) ◽  
pp. 743-748 ◽  
Author(s):  
Yun Yang ◽  
Li Zou ◽  
Yong Wan ◽  
Ke-Shu Xu ◽  
Jin-Xiang Zhang ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Dual Function ◽  
Guidance Cue

Characterization of axon guidance cue sensitivity of human embryonic stem cell-derived dopaminergic neurons

2010 ◽  
Vol 45 (4) ◽  
pp. 324-334 ◽  
Author(s):  
Branden J. Cord ◽  
Jie Li ◽  
Melissa Works ◽  
Susan K. McConnell ◽  
Theo Palmer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Axon Guidance ◽  
Dopaminergic Neurons ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Guidance Cue

scholarly journals Dual Function of NRP1 in Axon Guidance and Subcellular Target Recognition in Cerebellum

Neuron ◽  
2016 ◽  
Vol 91 (6) ◽  
pp. 1276-1291 ◽  
Author(s):  
Ludovic Telley ◽  
Christelle Cadilhac ◽  
Jean-Michel Cioni ◽  
Veronique Saywell ◽  
Céline Jahannault-Talignani ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Target Recognition ◽  
Dual Function ◽  
Subcellular Target

scholarly journals A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Nicholas P. Boyer ◽  
Laura E. McCormick ◽  
Shalini Menon ◽  
Fabio L. Urbina ◽  
Stephanie L. Gupton
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Ubiquitin Ligases ◽  
Critical Element ◽  
E3 Ubiquitin Ligases ◽  
Related Protein ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Neuronal Connections ◽  
Novel Model

Appropriate axon guidance is necessary to form accurate neuronal connections. Axon guidance cues that stimulate cytoskeletal reorganization within the growth cone direct axon navigation. Filopodia at the growth cone periphery have long been considered sensors for axon guidance cues, yet how they respond to extracellular cues remains ill defined. Our previous work found that the filopodial actin polymerase VASP and consequently filopodial stability are negatively regulated via nondegradative TRIM9-dependent ubiquitination. Appropriate VASP ubiquitination and deubiquitination are required for axon turning in response to the guidance cue netrin-1. Here we show that the TRIM9-related protein TRIM67 outcompetes TRIM9 for interacting with VASP and antagonizes TRIM9-dependent VASP ubiquitination. The surprising antagonistic roles of two closely related E3 ubiquitin ligases are required for netrin-1–dependent filopodial responses, axon turning and branching, and fiber tract formation. We suggest a novel model in which coordinated regulation of VASP ubiquitination by a pair of interfering ligases is a critical element of VASP dynamics, filopodial stability, and axon guidance.

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 Multiple Functions of Draxin/Netrin-1 Signaling in the Development of Neural Circuits in the Spinal Cord and the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Giasuddin Ahmed ◽  
Yohei Shinmyo
Keyword(s):  
Spinal Cord ◽  
Axon Guidance ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Deleted In Colorectal Cancer ◽  
Guidance Cue ◽  
Thalamocortical Projections ◽  
The Central Nervous System ◽  
Circuit Formation ◽  
The Brain

Axon guidance proteins play key roles in the formation of neural circuits during development. We previously identified an axon guidance cue, named draxin, that has no homology with other axon guidance proteins. Draxin is essential for the development of various neural circuits including the spinal cord commissure, corpus callosum, and thalamocortical projections. Draxin has been shown to not only control axon guidance through netrin-1 receptors, deleted in colorectal cancer (Dcc), and neogenin (Neo1) but also modulate netrin-1-mediated axon guidance and fasciculation. In this review, we summarize the multifaceted functions of draxin and netrin-1 signaling in neural circuit formation in the central nervous system. Furthermore, because recent studies suggest that the distributions and functions of axon guidance cues are highly regulated by glycoproteins such as Dystroglycan and Heparan sulfate proteoglycans, we discuss a possible function of glycoproteins in draxin/netrin-1-mediated axon guidance.

scholarly journals RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in C. elegans

2019 ◽  
Author(s):  
Mahekta R. Gujar ◽  
Aubrie M. Stricker ◽  
Erik A. Lundquist
Keyword(s):  
Axon Guidance ◽  
Growth Cone ◽  
Neural Circuit ◽  
Growth Cones ◽  
Negative Regulator ◽  
Microtubule Organization ◽  
C Elegans ◽  
Guidance Cue ◽  
Rho Gef

AbstractUNC-6/Netrin is a conserved axon guidance cue that directs growth cone migrations in the dorsal-ventral axis of C. elegans and in the vertebrate spinal cord. UNC-6/Netrin is expressed in ventral cells, and growth cones migrate ventrally toward or dorsally away from UNC-6/Netrin. Recent studies of growth cone behavior during outgrowth in vivo in C. elegans have led to a polarity/protrusion model in directed growth cone migration away from UNC-6/Netrin. In this model, UNC-6/Netrin first polarizes the growth cone via the UNC-5 receptor, leading to dorsally biased protrusion and F-actin accumulation. UNC-6/Netrin then regulates protrusion based on this polarity. The receptor UNC-40/DCC drives protrusion dorsally, away from the UNC-6/Netrin source, and the UNC-5 receptor inhibits protrusion ventrally, near the UNC-6/Netrin source, resulting in dorsal migration. UNC-5 inhibits protrusion in part by excluding microtubules from the growth cone, which are pro-protrusive. Here we report that the RHO-1/RhoA GTPase and its activator GEF RHGF-1 inhibit growth cone protrusion and MT accumulation in growth cones, similar to UNC-5. However, growth cone polarity of protrusion and F-actin were unaffected by RHO-1 and RHGF-1. Thus, RHO-1 signaling acts specifically as a negative regulator of protrusion and MT accumulation, and not polarity. Genetic interactions suggest that RHO-1 and RHGF-1 act with UNC-5, as well as with a parallel pathway, to regulate protrusion. The cytoskeletal interacting molecule UNC-33/CRMP was required for RHO-1 activity to inhibit MT accumulation, suggesting that UNC-33/CRMP might act downstream of RHO-1. In sum, these studies describe a new role of RHO-1 and RHGF-1 in regulation of growth cone protrusion by UNC-6/Netrin.Author SummaryNeural circuits are formed by precise connections between axons. During axon formation, the growth cone leads the axon to its proper target in a process called axon guidance. Growth cone outgrowth involves asymmetric protrusion driven by extracellular cues that stimulate and inhibit protrusion. How guidance cues regulate growth cone protrusion in neural circuit formation is incompletely understood. This work shows that the signaling molecule RHO-1 acts downstream of the UNC-6/Netrin guidance cue to inhibit growth cone protrusion in part by excluding microtubules from the growth cone, which are structural elements that drive protrusion.

scholarly journals Nell2 regulates the contralateral-versus-ipsilateral visual projection as a layer-specific positional cue

2018 ◽  
Author(s):  
Chizu Nakamoto ◽  
Elaine Durward ◽  
Masato Horie ◽  
Masaru Nakamoto
Keyword(s):  
Axon Guidance ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Retinal Ganglion ◽  
Guidance Cue ◽  
Retinal Axons ◽  
Visual Projection ◽  
Summary Statement ◽  
Retinogeniculate Projection ◽  
Dorsal Lateral Geniculate

SUMMARY STATEMENTNell2 is an ipsilateral layer-specific axon guidance cue in the visual thalamus and contributes to establishment of the eye-specific retinogeniculate projection by specifically inhibiting contralateral retinal axons.ABSTRACTIn mammals with binocular vision, retinal ganglion cell (RGC) axons from each eye project to eye-specific layers in the contralateral and ipsilateral dorsal lateral geniculate nucleus (dLGN). Although layer-specific axon guidance cues that discriminate contralateral and ipsilateral RGC axons have long been postulated as a key mechanism for development of the eye-specificretinogeniculate projection, the molecular nature of such cues has remained elusive. Here we show that the extracellular glycoprotein Nell2 (also known as Nel) is expressed in the dorsomedial region of the dLGN, which corresponds to the layer receiving ipsilateral RGC axons. In Nell2 mutant mice, contralateral RGC axons invaded the ipsilateral layer of the dLGN, and ipsilateral axons terminated in partially fragmented patches, forming a mosaic pattern of contralateral and ipsilateral axon termination zones. In vitro, Nell2 exerted inhibitory effects on contralateral, but not ipsilateral, RGC axons. These results provide evidence that Nell2 acts as a layer-specific positional label in the dLGN that discriminates contralateral and ipsilateral RGC axons, and that it plays essential roles in establishment of the eye-specific projection patterns in the retinogeniculate system.

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