Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling

Jaworski, Alexander; Tessier‐Lavigne, Marc

doi:10.1038/nn.3037

Cited by 82 publications

(88 citation statements)

References 14 publications

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“…Mammalian motoneurons differ from commissural neurons in that they co-express Robo1/2, Dcc and Slit2. In this context, Slit2 seems to have an autocrine function that controls motor axon fasciculation towards their muscle targets (Jaworski and Tessier-Lavigne, 2012). Within the spinal cord, Slit binding to Robo1/2 on motor axons silences Dcc function and prevents these axons from being attracted by netrin 1 at the floor plate (Bai et al, 2011).…”

Section: Slit-robo Signaling At the Spinal Cord Midlinementioning

confidence: 99%

Slit-Robo signaling

2016

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Slits are secreted proteins that bind to Roundabout (Robo) receptors. Slit-Robo signaling is best known for mediating axon repulsion in the developing nervous system. However, in recent years the functional repertoire of Slits and Robo has expanded tremendously and Slit-Robo signaling has been linked to roles in neurogenesis, angiogenesis and cancer progression among other processes. Likewise, our mechanistic understanding of Slit-Robo signaling has progressed enormously. Here, we summarize new insights into Slit-Robo evolutionary and system-dependent diversity, receptor-ligand interactions, signaling crosstalk and receptor activation.

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Section: Slit-robo Signaling At the Spinal Cord Midlinementioning

confidence: 99%

Slit-Robo signaling

2016

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“…In our study, the increase of the NgR1-immunohistochemical signal in the highly Nogo-A-positive RGCs of Cnp-Cre þ / À xRtn4 flox/flox KOs could reflect cisinteractions between the ligand and receptor. At the cell membrane, the sequestration and inactivation of ligands by cis-binding to adjacent receptors has previously been described to prevent trans-activation in the case of guidance molecules such as Ephrins, 16 semaphorins 17 or Slit-Robo, 56 but also for the Notch signaling pathway. 57 The co-expression of Nogo-A and NgR1 in RGCs of Cnp-Cre þ / À xRtn4 flox/flox KO mice could prevent downstream activation of Rho-A after ONC and Nogo-A overexpression in F11 cells could partially counteract neurite outgrowth inhibition induced by Nogo-A-D20.…”

Section: Moreover Inflammation-inducing Agents Such As Zymosan or Pamentioning

confidence: 99%

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

et al. 2014

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Nogo-A is a well-known myelin-enriched inhibitory protein for axonal growth and regeneration in the central nervous system (CNS). Besides oligodendrocytes, our previous data revealed that Nogo-A is also expressed in subpopulations of neurons including retinal ganglion cells, in which it can have a positive role in the neuronal growth response after injury, through an unclear mechanism. In the present study, we analyzed the opposite roles of glial versus neuronal Nogo-A in the injured visual system. To this aim, we created oligodendrocyte (Cnp-Cre þ / À xRtn4/Nogo-A flox/flox ) and neuron-specific (Thy1-Cre tg þ xRtn4 flox/flox ) conditional Nogo-A knock-out (KO) mouse lines. Following complete intraorbital optic nerve crush, both spontaneous and inflammation-mediated axonal outgrowth was increased in the optic nerves of the glia-specific Nogo-A KO mice. In contrast, neuron-specific deletion of Nogo-A in a KO mouse line or after acute gene recombination in retinal ganglion cells mediated by adeno-associated virus serotype 2.Cre virus injection in Rtn4 flox/flox animals decreased axon sprouting in the injured optic nerve. These results therefore show that selective ablation of Nogo-A in oligodendrocytes and myelin in the optic nerve is more effective at enhancing regrowth of injured axons than what has previously been observed in conventional, complete Nogo-A KO mice. Our data also suggest that neuronal Nogo-A in retinal ganglion cells could participate in enhancing axonal sprouting, possibly by cis-interaction with Nogo receptors at the cell membrane that may counteract trans-Nogo-A signaling. We propose that inactivating Nogo-A in glia while preserving neuronal Nogo-A expression may be a successful strategy to promote axonal regeneration in the CNS.

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“…Slit2 and Robo1 are expressed in phrenic motor neurons and myoblasts forming costal muscles, respectively, during diaphragm development Recent findings have revealed that Sli-Robo signaling does not only have a direct effect on phrenic nerve fasciculation (Jaworski and Tessier-Lavigne, 2012), but that Slit proteins, released by the sclerotome, can also repel pioneering myoblasts during early development of avian embryos (Halperin-Barlev and Kalcheim, 2011). At later stages, migrating pioneering myoblasts are attracted by Slit proteins released by the tendon to guide them to their final destination in Drosophila (Kramer, 2001).…”

Section: Misprojecting Phrenic Axons Innervate Ectopic Muscles In Thementioning

confidence: 99%

“…Nevertheless, it is unlikely that axon-derived Slit1 has a major role in vivo, as it is not expressed in phrenic motor neurons during the innervation of the diaphragm (Jaworski and Tessier-Lavigne, 2012).…”

Section: Diaphragm Myoblasts From Costal Muscles Are Attracted By Slitsmentioning

confidence: 99%

“…Well-known members of axon guidance cue families, such as Slit2 and its receptors Robo1 and Robo2 have been shown to be involved not only in targeting of the phrenic nerves towards the pleuroperitoneal folds (PPFs), from which the diaphragm muscle arises, but also in phrenic nerve fasciculation and innervation of the diaphragm musculature (Jaworski and Tessier-Lavigne, 2012). Both the receptor tyrosine kinase ErbB2, and Unc5c, a netrin receptor, were proven essential for the stabilization of neuro-muscular junctions (NMJs) or appropriate innervation of the costal muscle proportion, respectively (Burgess et al, 2006;Lin et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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The role of Sema3–Npn-1 signaling during diaphragm innervation and muscle development

et al. 2016

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Correct innervation of the main respiratory muscle in mammals, namely the thoracic diaphragm, is a crucial pre-requisite for the functionality of this muscle and the viability of the entire organism. Systemic impairment of Sema3A-Npn-1 (Npn-1 is also known as NRP1) signaling causes excessive branching of phrenic nerves in the diaphragm and into the central tendon region, where the majority of misguided axons innervate ectopic musculature. To elucidate whether these ectopic muscles are a result of misguidance of myoblast precursors due to the loss of Sema3A-Npn-1 signaling, we conditionally ablated Npn-1 in somatic motor neurons, which led to a similar phenotype of phrenic nerve defasciculation and, intriguingly, also formation of innervated ectopic muscles. We therefore hypothesize that ectopic myocyte fusion is caused by additional factors released by misprojecting growth cones. Slit2 and its Robo receptors are expressed by phrenic motor axons and migrating myoblasts, respectively, during innervation of the diaphragm. In vitro analyses revealed a chemoattractant effect of Slit2 on primary diaphragm myoblasts. Thus, we postulate that factors released by motor neuron growth cones have an influence on the migration properties of myoblasts during establishment of the diaphragm.

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Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling

Cited by 82 publications

References 14 publications

Slit-Robo signaling

Slit-Robo signaling

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

The role of Sema3–Npn-1 signaling during diaphragm innervation and muscle development

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