RETRACTED: Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge

Dun, Xin‐Peng; Carr, Lauren; Woodley, Patricia K.; Barry, Riordan W.; Drake, Louisa K.; Mindos, Thomas; Roberts, Sheridan L.; Lloyd, Alison C.; Parkinson, David B.

doi:10.1016/j.celrep.2018.12.081

Cited by 66 publications

(94 citation statements)

References 43 publications

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“…In their study, Dun et al showed that Sox2 regulates Robo1 receptor expression in migrating SCs and that macrophages in the outermost layer of the nerve bridge secrete high levels of its ligand Slit3. Further gene ablation experiments confirm that Slit3/Robo1 repulsive signal is crucial for SC migration trajectory and correct nerve bridge formation following nerve transection [115]. Taken together these results suggest that the coordinated action of different cell types and the combined function of multiple axon guidance molecules is necessary for a correct nerve bridge tissue formation and precise axon targeting in the nerve bridge.…”

Section: Sox2 and Nerve Bridge Tissue Formationmentioning

confidence: 57%

“…Indeed, it has been shown that both pharmacological inhibition and genetical ablation of EphB2 resulted in significantly shorter and less organized regrowing axons as compared to untreated and wild type animals [26]. Moreover, Dun et al [115], showed that by regulating the Slit3/Robo1 pathway, Sox2 is also critical for SC migration in the nerve bridge and axon pathfinding after nerve injury. Indeed, this study shows how Sox2 loss of function leads to ectopic SC migration and to the inability to form proper SC cords connecting the nerves stumps [115].…”

Section: Sox2 and Nerve Bridge Tissue Formationmentioning

confidence: 99%

“…Moreover, Dun et al [115], showed that by regulating the Slit3/Robo1 pathway, Sox2 is also critical for SC migration in the nerve bridge and axon pathfinding after nerve injury. Indeed, this study shows how Sox2 loss of function leads to ectopic SC migration and to the inability to form proper SC cords connecting the nerves stumps [115]. It has previously been shown that Slit-Robo interaction is crucial for axon guidance and serves as a repulsive signaling to control axon pathfinding and neuronal migration during nervous system development [116].…”

Section: Sox2 and Nerve Bridge Tissue Formationmentioning

confidence: 99%

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Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury

Nocera

Jacob

2020

Cell. Mol. Life Sci.

279

204

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The great plasticity of Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), is a critical feature in the context of peripheral nerve regeneration following traumatic injuries and peripheral neuropathies. After a nerve damage, SCs are rapidly activated by injury-induced signals and respond by entering the repair program. During the repair program, SCs undergo dynamic cell reprogramming and morphogenic changes aimed at promoting nerve regeneration and functional recovery. SCs convert into a repair phenotype, activate negative regulators of myelination and demyelinate the damaged nerve. Moreover, they express many genes typical of their immature state as well as numerous de-novo genes. These genes modulate and drive the regeneration process by promoting neuronal survival, damaged axon disintegration, myelin clearance, axonal regrowth and guidance to their former target, and by finally remyelinating the regenerated axon. Many signaling pathways, transcriptional regulators and epigenetic mechanisms regulate these events. In this review, we discuss the main steps of the repair program with a particular focus on the molecular mechanisms that regulate SC plasticity following peripheral nerve injury.

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Section: Sox2 and Nerve Bridge Tissue Formationmentioning

confidence: 57%

Section: Sox2 and Nerve Bridge Tissue Formationmentioning

confidence: 99%

Section: Sox2 and Nerve Bridge Tissue Formationmentioning

confidence: 99%

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Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury

Nocera

Jacob

2020

Cell. Mol. Life Sci.

279

204

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“…These innate immune cells provide critical phagocytic functions . But additionally, these innate immune cells provide other functions essential to nerve regeneration, including re‐myelination and functional recovery, which are not yet entirely understood, After this Wallerian degeneration process is complete, SCs progressively assume long processes and align on the basal lamina of the intact distal nerve environment (bands of Bungner), providing a permissive growth environment for the regenerating axons that emerge from the proximal nerve stump . As axon growth proceeds from proximal to distal nerve, remyelination of the axons is initiated primarily by axon‐derived neuregulin‐1 signaling through SCs’ ErbB receptors .…”

Section: Biology Of Nerve Regeneration Across a Defectmentioning

confidence: 99%

Advances in the repair of segmental nerve injuries and trends in reconstruction

2020

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Despite advances in surgery, the reconstruction of segmental nerve injuries continues to pose challenges. In this review, current neurobiology regarding regeneration across a nerve defect is discussed in detail. Recent findings include the complex roles of nonneuronal cells in nerve defect regeneration, such as the role of the innate immune system in angiogenesis and how Schwann cells migrate within the defect. Clinically, the repair of nerve defects is still best served by using nerve autografts with the exception of small, noncritical sensory nerve defects, which can be repaired using autograft alternatives, such as processed or acellular nerve allografts. Given current clinical limits for when alternatives can be used, advanced solutions to repair nerve defects demonstrated in animals are highlighted. These highlights include alternatives designed with novel topology and materials, delivery of drugs specifically known to accelerate axon growth, and greater attention to the role of the immune system. K E Y W O R D S acellular nerve allograft, autograft, nerve gap, nerve guidance conduit, peripheral nerve 2 | BIOLOGY OF NERVE REGENERATION ACROSS A DEFECT Peripheral nerve is capable of robust regeneration following injury. The molecular and cellular mechanisms have primarily been studied in rodent models. Following injury, neurons and their axons and the nonneuronal cellular environment distal to the injury undergo immediate morphological and molecular changes. Within the axon, there is a rapid influx of ions, principally calcium, as well as a disruption of transport proteins signaling a disruption to homeostasis with its end-organ. This multifactorial injury response from axon damage is rapidly transported to the neuron cell Abbreviations: ANA, acellular nerve allograft; ECM, extracellular matrix; FDA, Food and Drug Administration; FK506, tacrolimus; GDNF, glial cell line-derived neurotrophic factor; GFRα1, glial cell line-derived neurotrophic factor family receptor alpha-1; MRC, Medical Research

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“…The PLP-GFP mouse transgenic strain was used in this study (Mallon et al, 2002). Originally made to label oligodendrocytes in the central nervous system driven GFP expression by the mouse myelin PLP gene promoter, the PLP-GFP mice also express cytoplasmic GFP in both myelinating and non-myelinating Schwann cells of the peripheral nerves (Mallon et al, 2002;Stierli et al, 2018;Dun et al, 2019). All work involving animals was performed according to Home Office regulation under the UK Animals (Scientific Procedures) Act 1986.…”

Section: Animal Husbandry and Peripheral Nerve Surgerymentioning

confidence: 99%

Analysis of Schwann Cell Migration and Axon Regeneration Following Nerve Injury in the Sciatic Nerve Bridge

Chen

Parkinson

et al. 2019

Front. Mol. Neurosci.

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While it is proposed that interaction between Schwann cells and axons is key for successful nerve regeneration, the behavior of Schwann cells migrating into a nerve gap following a transection injury and how migrating Schwann cells interact with regenerating axons within the nerve bridge has not been studied in detail. In this study, we combine the use of our whole-mount sciatic nerve staining with the use of a proteolipid proteingreen fluorescent protein (PLP-GFP) mouse model to mark Schwann cells and have examined the behavior of migrating Schwann cells and regenerating axons in the sciatic nerve gap following a nerve transection injury. We show here that Schwann cell migration from both nerve stumps starts later than the regrowth of axons from the proximal nerve stump. The first migrating Schwann cells are only observed 4 days following mouse sciatic nerve transection injury. Schwann cells migrating from the proximal nerve stump overtake regenerating axons on day 5 and form Schwann cell cords within the nerve bridge by 7 days post-transection injury. Regenerating axons begin to attach to migrating Schwann cells on day 6 and then follow their trajectory navigating across the nerve gap. We also observe that Schwann cell cords in the nerve bridge are not wide enough to guide all the regenerating axons across the nerve bridge, resulting in regenerating axons growing along the outside of both proximal and distal nerve stumps. From this analysis, we demonstrate that Schwann cells play a crucial role in controlling the directionality and speed of axon regeneration across the nerve gap. We also demonstrate that the use of the PLP-GFP mouse model labeling Schwann cells together with the whole sciatic nerve axon staining technique is a useful research model to study the process of peripheral nerve regeneration.

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RETRACTED: Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge

Cited by 66 publications

References 43 publications

Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury

Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury

Advances in the repair of segmental nerve injuries and trends in reconstruction

Analysis of Schwann Cell Migration and Axon Regeneration Following Nerve Injury in the Sciatic Nerve Bridge

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