The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals

Law, Chris; Kirby, Rebecca J.; Aghamohammadzadeh, Soheil; Furley, Andrew J.

doi:10.1242/dev.009019

Cited by 47 publications

(70 citation statements)

References 53 publications

(128 reference statements)

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“…The net effect of this model would be a switch in axon responsiveness that would allow axons to first reach, and then be retained within, their correct final targets. This model is analogous to the switch models previously proposed to occur at axon intermediate targets (Butler and Tear, 2007;Chen et al, 2008;He et al, 2002;Law et al, 2008;Nawabi et al, 2010;Parra and Zou, 2009;Tessier-Lavigne and Goodman, 1996), but in this case the switch in responsiveness would occur at the final target.…”

Section: Role Of Type III Nrg1 In Sema3a Responsivenessmentioning

confidence: 55%

“…In addition to guidance cues that can steer the growth cone, axon pathfinding involves extracellular signals that regulate whether an axon reacts to a guidance cue with an attractant response, a repellent response, or no response (Butler and Tear, 2007;Chen et al, 2008;He et al, 2002;Law et al, 2008;Parra and Zou, 2009;Tessier-Lavigne and Goodman, 1996). Sema3A is a diffusible repellent guidance cue expressed in the ventral horn and periphery that selectively repels axons of Ngf-dependent sensory neurons, preventing them from overshooting their normal targets in the dorsal horn (Fu et al, 2000;Messersmith et al, 1995;Pond et al, 2002;Puschel et al, 1996;Wright et al, 1995).…”

Section: Role Of Type III Nrg1 In Sema3a Responsivenessmentioning

confidence: 99%

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Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery

et al. 2011

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SUMMARYSensory axons must develop appropriate connections with both central and peripheral targets. Whereas the peripheral cues have provided a classic model for neuron survival and guidance, less is known about the central cues or the coordination of central and peripheral connectivity. Here we find that type III Nrg1, in addition to its known effect on neuron survival, regulates axon pathfinding. In type III Nrg1 -/-mice, death of TrkA + nociceptive/thermoreceptive neurons was increased, and could be rescued by Bax elimination. In the Bax and type III Nrg1 double mutants, axon pathfinding abnormalities were seen for TrkA + neurons both in cutaneous peripheral targets and in spinal cord central targets. Axon guidance phenotypes in the spinal cord included penetration of axons into ventral regions from which they would normally be repelled by Sema3A. Accordingly, sensory neurons from type III Nrg1 -/-mice were unresponsive to the repellent effects of Sema3A in vitro, which might account, at least in part, for the central projection phenotype, and demonstrates an effect of type III Nrg1 on guidance cue responsiveness in neurons. Moreover, stimulation of type III Nrg1 back-signaling in cultured sensory neurons was found to regulate axonal levels of the Sema3A receptor neuropilin 1. These results reveal a molecular mechanism whereby type III Nrg1 signaling can regulate the responsiveness of neurons to a guidance cue, and show that type III Nrg1 is required for normal sensory neuron survival and axon pathfinding in both central and peripheral targets.

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Section: Role Of Type III Nrg1 In Sema3a Responsivenessmentioning

confidence: 55%

Section: Role Of Type III Nrg1 In Sema3a Responsivenessmentioning

confidence: 99%

Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery

et al. 2011

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“…1b,c). TAG-1 is a cell adhesion molecule that is highly expressed in sensory growth cones and is essential for Sema3A signalling 32 . Our analysis of E13, E14 and E15 sensory growth cones indicated a gradual increase in TAG-1 immunofluorescence in both , to promote growth of proprioceptive or cutaneous axons, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The receptor complex for the axonal repellant Semaphorin3A (Sema3A) comprises two core elements: Neuropilin-1 (Nrp1), which binds the ligand but lacks signalling capabilities [25][26][27] , and type-A Plexin, which transmits the signal 28,29 . Two other components implicated in activation of the response to Sema3A and endocytosis of the receptor complex, respectively, are the L1 cell adhesion molecule (L1-CAM) and the transiently expressed axonal glycoprotein-1 (TAG-1) [30][31][32][33] .…”

mentioning

confidence: 99%

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A

et al. 2014

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During embryonic development, axons can gain and lose sensitivity to guidance cues, and this flexibility is essential for the correct wiring of the nervous system. Yet, the underlying molecular mechanisms are largely unknown. Here we show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease) metalloproteases promotes murine sensory axons loss of responsiveness to the chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in sensory axons. Moreover, this is correlated with gain of repulsive response to Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM knockouts that are consistent with enhanced response to Sema3A. Our results provide the first evidence for involvement of ADAMs in regulating developmental switch in responsiveness to axonal guidance cues.

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“…These examples are not the norm as in the absence of single CAMs or ECM components, few defects are normally observed in neurons in axonal pathfinding or organization, such as in the loss of b integrin in a conditional knockout mouse (Schwander et al 2004). Further, these mutant phenotypes may not be explained by the loss of adhesive interactions per se, but instead may be ascribed to the proposed role of CAMs such as L1 or integrins as crucial accessory receptors involved in semaphorin signaling (Castellani et al 2000;Pasterkamp et al 2003;Bechara et al 2007;Wolman et al 2007;Law et al 2008;Wang et al 2008).…”

Section: Adhesive Cuesmentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

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Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment.T his article provides an overview of how growth cones respond to the cellular substrata and molecular cues they encounter as they extend through the developing nervous system. It elaborates on the primer by Kolodkin and TessierLavigne (2010) and touches on many of the topics covered in greater detail in the articles that follow. The first sections describe how axons extend in a directed manner, the substrata on which they grow, interactions between pioneer and follower axons, and growth cone behaviors in emerging tracts and at decision points. The subsequent sections discuss examples of specific cues, their distributions, how their distributions are determined, and how growth cones integrate multiple cues during pathfinding. AXONS EXTEND IN VIVO IN A DIRECTED MANNERThe first person to visualize the growing tips of axons, Ramon y Cajal, recognized that axons for the most part grow very efficiently towards their ultimate targets. He was a strong advocate for axons finding their way in response to chemotactic cues:"If one admits that neuroblasts are endowed with chemotactic properties, then one might also imagine that they are capable of ameboid movements, initiated by factors secreted from epithelial, neural, or mesodermal elements. As a result, their processes may be oriented in the direction of chemical gradients, and thus guided to the secreting cells" (Ramon y Cajal 1892; trans. English, 1995).This surprisingly modern outlook emphasizing directed guidance was temporarily derailed by the views of Weiss during the 1920s and 1930s. He first argued that functional specificity did not arise as a consequence of specific axonal connections (Weiss 1936), and later argued that nonspecific mechanical guidance cues play a predominant role in guiding axons and organizing them into nerves and tracts

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The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals

Cited by 47 publications

References 53 publications

Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery

Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A

Cellular Strategies of Axonal Pathfinding

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