Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types

Villegas, Rosario; Martin, Seanna M.; O’Donnell, Kelley C.; Carrillo, Simón A.; Sagasti, Alvaro; Allende, Miguel L.

doi:10.1186/1749-8104-7-19

Cited by 73 publications

(92 citation statements)

References 70 publications

(106 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although Schwann cells play a major role in the guidance of regenerating axons, as evidenced by the close apposition of the latter along the former, we observed that the absence of Schwann cells has but little effect on the latency of reinnervation. This is consistent with a similar observation made during early larval life (10). Thus, the promoting effect is likely to involve a local change in axonal properties, rather than an increased attractiveness of denervated Schwann cells.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Dynamics of axonal regeneration in adult and aging zebrafish reveal the promoting effect of a first lesion

Graciarena

Dambly‐Chaudière

Ghysen

2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Axonal regeneration is a major issue in the maintenance of adult nervous systems, both after nerve injuries and in neurodegenerative diseases. However, studying this process in vivo is difficult or even impossible in most vertebrates. Here we show that the posterior lateral line (PLL) of zebrafish is a suitable system to study axonal regeneration in vivo because of both the superficial location and reproducible spatial arrangement of neurons and targets, and the possibility of following reinnervation in live fish on a daily basis. Axonal regeneration after nerve cut has been demonstrated in this system during the first few days of life, leading to complete regeneration within 24 h. However, the potential for PLL nerve regeneration has not been tested yet beyond the early larval stage. We explore the regeneration potential and dynamics of the PLL nerve in adult zebrafish and report that regeneration occurs throughout adulthood. We observed that irregularities in the original branching pattern are faithfully reproduced after regeneration, suggesting that regenerating axons follow the path laid down by the original nerve branches. We quantified the extent of target reinnervation after a nerve cut and found that the latency before the nerve regenerates increases with age. This latency is reduced after a second nerve cut at all ages, suggesting that a regeneration-promoting factor induced by the first cut facilitates regeneration on a second cut. We provide evidence that this factor remains present at the site of the first lesion for several days and is intrinsic to the neurons.Schwann cells | axonogenesis | neuromast | sensory system T he potential of adult neurons to regenerate their axons and to reinnervate target organs after injury is not as well understood as early axonogenesis. Whether and how this capability is modified on aging is an even less explored area. In all vertebrates studied so far, neurons of the peripheral nervous system retain the ability to reextend peripheral axons and reestablish functional connections. This ability is thought to involve intrinsic mechanisms of repair as well as extrinsic signals from the local environment, mostly coming from Schwann cells and macrophages (1).The posterior lateral line (PLL) of fish is a convenient yet unexplored sensory system to address the issue of axonal regeneration throughout adulthood. The PLL comprises a set of superficial mechanosensory organs called neuromasts, which are distributed over the body and tail. Neuromasts are composed of a core of mechanosensory hair cells providing information about the local water flow, surrounded by accessory cells. The afferent neurons innervating neuromasts are clustered in a ganglion posterior to the otic vesicle, and their peripheral axons extend toward the tail, right under the skin. This sensory system is involved in a large repertoire of behaviors (2).The juvenile PLL of zebrafish comprises four lines of neuromasts that extend at different dorsoventral levels, totaling about 50 organs (3). This pattern is estab...

show abstract

Section: Discussionsupporting

confidence: 92%

“…Regenerating axons follow either the Schwann cells that ensheathe the nerve (10) or the interneuromast cells that extend between consecutive neuromasts (11). PLL nerve regeneration has not yet been addressed beyond the early larval stage.…”

mentioning

confidence: 99%

Dynamics of axonal regeneration in adult and aging zebrafish reveal the promoting effect of a first lesion

Graciarena

Dambly‐Chaudière

Ghysen

2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…2 B′-D′, yellow pseudocolored cells). Previously, we showed that macrophages and/or microglia responded to rod cell loss (12); however, the presence of pigmented cells (i.e., iridophores) limited our ability to track individual cell behaviors accurately. Here we resolved this issue by using a mutant lacking iridophores (roy orbison).…”

Section: Resultsmentioning

confidence: 99%

“…Macrophages are efficient phagocytes that contribute to the clearance of dead cells (64). Moreover, macrophages have been implicated as beneficial to healing/regenerative processes in a diverse set of injury paradigms including muscle (65), limb (8,9), lateral line (12,66), heart (10), brain (11,38), spinal cord (67,68), and retina (33, 69). However, there is controversy over the extent to which monocyte-derived macrophages are involved in CNS degenerative diseases.…”

Section: Peripheral Macrophages Are Responsive To Rod Cell Death But mentioning

confidence: 99%

“…Recent studies have implicated innate immune cells in regulating tissue regeneration in the limb (8,9), heart (10), and brain (11). In addition, discrete immune cell types react to selective neuronal cell ablation in the peripheral (12) and central nervous systems in regenerative species (13)(14)(15). However, whether the immune system regulates regeneration following the selective loss of individual neuronal cell types (i.e., in paradigms akin to neurodegenerative disease) remains unknown.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

White¹,

Sengupta²,

Saxena³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

153

218

View full text Add to dashboard Cite

Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation, and (iii) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions. retina | microglia | glucocorticoid | regeneration | macrophage N eurodegenerative diseases are caused by the loss of discrete neuronal cell types. The goal of regenerative medicine is to reverse this process. One strategy for doing so involves harnessing the regenerative potential of endogenous neural stem cells. Unfortunately, although adult neural stem cells exist in the mammalian CNS, innate potentials for neuronal repair remain dormant in the absence of exogenous stimulation. Conversely, many other species are endowed with remarkable capacities for neuronal regeneration. For instance, in the zebrafish eye, retinal Müller glia (MG) cells can dedifferentiate to a stem cell-like state and give rise to progenitors that replace lost neurons and restore visual function (1, 2). Intriguingly, human MG cells are able to give rise to new neurons in culture (3) that can restore visual function when transplanted into mammalian disease models (4), suggesting that human MG retain a stem cell-like capacity for mediating retinal repair. Mechanisms controlling the regenerative potential of MG are therefore of great interest. We and others study zebrafish to learn more about how retinal regeneration is cont...

show abstract

Engulfment Genes Promote Neuronal Regeneration in Caenorhabditis Elegans: Two Divergent But Complementary Views

Chang

Hisamoto

2020

BioEssays

View full text Add to dashboard Cite

Axon regeneration is a conserved process across the animal kingdom. Recent studies using the soil worm Caenorhabditis elegans as a model system revealed that machineries regulating engulfment of dying cells also control axon regeneration and axon debris removal. In this review, we examine the relationships between the engulfment machinery and the biological processes triggered by axon injury and subsequent axon regeneration drawn from divergent views. In one study, it was found that engulfing cells directly promote axon regeneration. In this context, CED-1 (Drosophila Draper/mouse MEGF10), an engulfment protein expressed on the surface of engulfing cells, functions as a receptor for axon debris removal and as an adhesion molecule for axon regeneration. In other studies, it was shown that those engulfment genes, previously known to function within the engulfing cells for cell corpse removal, can have a cell-autonomous "non-engulfing cell" role in axon regeneration. Together, these findings suggest that engulfment genes are repurposed for neuronal regeneration by acting in both engulfing cells and regenerating neurons.

show abstract

Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types

Cited by 73 publications

References 70 publications

Dynamics of axonal regeneration in adult and aging zebrafish reveal the promoting effect of a first lesion

Dynamics of axonal regeneration in adult and aging zebrafish reveal the promoting effect of a first lesion

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

Engulfment Genes Promote Neuronal Regeneration in Caenorhabditis Elegans: Two Divergent But Complementary Views

Contact Info

Product

Resources

About