Ryk controls remapping of motor cortex during functional recovery after spinal cord injury

Hollis, Edmund R.; Ishiko, Nao; Yu, Ting; Lu, Chin Chun; Haimovich, Ariela; Tolentino, Kristine; Richman, Alisha; Tury, Anna; Wang, Shih Hsiu; Pessian, Maysam; Jo, Euna; Kolodkin, Alex L.; Zou, Yimin

doi:10.1038/nn.4282

Cited by 76 publications

(72 citation statements)

References 35 publications

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“…Using optogenetic approaches, it was found that cortical areas dedicated to eliciting motor behaviors in the limbs were re‐mapped after forelimb training and C5 spinal cord injury. Ryk‐deleted mice had a larger cortical area involved in flexor (triceps) function and an overall increase in area dedicated to limb movement compared with control mice (Hollis et al, ). This work shows that an understanding of how axon guidance molecules exert their functions during development can lead to the conception of new strategies for enhancing repair and plasticity in the injured adult nervous system.…”

Section: Guidance Cuesmentioning

confidence: 99%

Maximizing functional axon repair in the injured central nervous system: Lessons from neuronal development

Kaplan

Bueno

Hua

et al. 2017

Developmental Dynamics

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The failure of damaged axons to regrow underlies disability in central nervous system injury and disease. Therapies that stimulate axon repair will be critical to restore function. Extensive axon regeneration can be induced by manipulation of oncogenes and tumor suppressors; however, it has been difficult to translate this into functional recovery in models of spinal cord injury. The current challenge is to maximize the functional integration of regenerating axons to recover motor and sensory behaviors. Insights into axonal growth and wiring during nervous system development are helping guide new approaches to boost regeneration and functional connectivity after injury in the mature nervous system. Here we discuss our current understanding of axonal behavior after injury and prospects for the development of drugs to optimize axon regeneration and functional recovery after CNS injury.

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Section: Guidance Cuesmentioning

confidence: 99%

Maximizing functional axon repair in the injured central nervous system: Lessons from neuronal development

Kaplan

Bueno

Hua

et al. 2017

Developmental Dynamics

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“…Ryk plays critical functions in Wnt‐mediated axon guidance, as first demonstrated for the Derailed receptor, the Drosophila homolog of Ryk (Yoshikawa et al, ). Studies in vertebrate systems have cemented Ryk's critical role as a regulator of neurite outgrowth, acting largely as repulsive cue that inhibits axon growth (Liu et al, ; Schmitt et al, ; Liu et al, ; Hollis et al, ) and dendritic arborization (Lanoue et al, ). In addition, Ryk has also been implicated in mediating neurite outgrowth (Lu et al, ).…”

Section: Introductionmentioning

confidence: 99%

Wnt/β‐catenin signaling during early vertebrate neural development

Brafman

Willert

2017

Developmental Neurobiology

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The vertebrate central nervous (CNS) is comprised of vast number of distinct cell types arranged in a highly organized manner. This high degree of complexity is achieved by cellular communication, including direct cell-cell contact, cell-matrix interactions, and cell-growth factor signaling. Among the several developmental signals controlling the development of the CNS, Wnt proteins have emerged as particularly critical and, hence, have captivated the attention of many researchers. With Wnts’ evolutionarily conserved function as primordial symmetry breaking signals, these proteins and their downstream effects are responsible for simultaneously establishing cellular diversity and tissue organization. With their expansive repertoire of secreted agonists and antagonists, cell surface receptors, signaling cascades and downstream biological effects, Wnts are ideally suited to control the complex processes underlying vertebrate neural development. In this review, we will describe the mechanisms by which Wnts exert their potent effects on cells and tissues and highlight the many roles of Wnt signaling during neural development, starting from the initial induction of the neural plate, the subsequent patterning along the embryonic axes, to the intricately organized structure of the CNS.

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“…Our results reinforce previous studies (Wang et al 2018) documenting the power of retro-AAV, tissue clearing, and light sheet imaging for obtaining quantitative and complete identification of the components of the CST. Also, our data on the normal projection patterns of CST axons from different parts of the cortex to different levels and laminae of the spinal cord provide novel insights into topographic specificity of normal CST projections, which will aid in identifying differences in projection patterns in mice carrying mutations, in detecting changes in patterns of projection due to regenerative growth following injury (Hollis et al 2016) and form part of the basis for comparisons of CST projection patterns between strains and species.…”

Section: Discussionmentioning

confidence: 98%

Rostro-caudal specificity of corticospinal tract projections in mice

Steward

Yee

Metcalfe

et al. 2020

Preprint

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Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT-reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex, the rostral forebrain area (RFA), and a region in the lateral cortex near the barrel field. Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the RFA or lateral cortex. With BDA injections into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic-sacral levels. With BDA injections into the RFA and lateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae; Axons from lateral sensorimotor cortex terminated primarily in deep layers of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.SIGNIFICANCEMice are used extensively for studies of regeneration following spinal cord injury because of the ability to create genetic modifications to explore ways to enhance repair and enable axon regeneration. A particular focus has been the corticospinal tract (CST) because of its importance for voluntary motor function. Here, we document features of the rostro-caudal specificity of CST

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Ryk controls remapping of motor cortex during functional recovery after spinal cord injury

Cited by 76 publications

References 35 publications

Maximizing functional axon repair in the injured central nervous system: Lessons from neuronal development

Maximizing functional axon repair in the injured central nervous system: Lessons from neuronal development

Wnt/β‐catenin signaling during early vertebrate neural development

Rostro-caudal specificity of corticospinal tract projections in mice

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