Know How to Regrow—Axon Regeneration in the Zebrafish Spinal Cord

Tsata, Vasiliki; Wehner, Daniel

doi:10.3390/cells10061404

Cited by 15 publications

(11 citation statements)

References 138 publications

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“…Strangely, the situation is quite different in fish and salamanders that have the capacity for long-distance axon regeneration and functional recovery after spinal cord injury. For instance, in the zebrafish, a spinal cord injury is followed by an immediate loss of function at the injury site, but in the long run, recovery is observed, associated with a complex response involving multiple cellular pathways and morphological changes (Tsata and Wehner 2021 ). Clearly, this is an extremely complex process, and there is an increasing understanding that mechanics has a role to play in it.…”

Section: Perspectives Challenges and Opportunitiesmentioning

confidence: 99%

Mathematical models of neuronal growth

Oliveri

Goriely

2022

Biomech Model Mechanobiol

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The establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites—axons and dendrites—to meet other neurons and interconnect. Therefore, these neurites need to migrate, grow, branch and find the correct path to their target by processing sensory cues from their environment. These processes rely on many coupled biophysical effects including elasticity, viscosity, growth, active forces, chemical signaling, adhesion and cellular transport. Mathematical models offer a direct way to test hypotheses and understand the underlying mechanisms responsible for neuron development. Here, we critically review the main models of neurite growth and morphogenesis from a mathematical viewpoint. We present different models for growth, guidance and morphogenesis, with a particular emphasis on mechanics and mechanisms, and on simple mathematical models that can be partially treated analytically.

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Section: Perspectives Challenges and Opportunitiesmentioning

confidence: 99%

Mathematical models of neuronal growth

Oliveri

Goriely

2022

Biomech Model Mechanobiol

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“…In the zebrafish central nervous system, it has been shown that acute inflammation is required for the proper induction of regenerative neurogenesis from neural stem cells ( Kyritsis et al, 2012 ; Tsarouchas et al, 2018 ; Silva et al, 2020 ). In particular, the cellular and molecular events during spinal cord regeneration have been dissected in great detail ( Tsata and Wehner, 2021 ). Upon injury, peripheral neutrophils invade the lesion side immediately followed by macrophages, which play a pivotal role in the subsequent functional regeneration, by producing tumor necrosis factor α and controlling interleukin-1 β-mediated inflammation ( Tsarouchas et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion

Schwarzer

Rekhade

Machate

et al. 2022

Front. Cell Dev. Biol.

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Sensorineural hearing loss is caused by the loss of sensory hair cells and/or their innervating neurons within the inner ear and affects millions of people worldwide. In mammals, including humans, the underlying cell types are only produced during fetal stages making loss of these cells and the resulting consequences irreversible. In contrast, zebrafish produce sensory hair cells throughout life and additionally possess the remarkable capacity to regenerate them upon lesion. Recently, we showed that also inner ear neurogenesis continues to take place in the zebrafish statoacoustic ganglion (SAG) well into adulthood. The neurogenic niche displays presumptive stem cells, proliferating Neurod-positive progenitors and a high level of neurogenesis at juvenile stages. It turns dormant at adult stages with only a few proliferating presumptive stem cells, no proliferating Neurod-positive progenitors, and very low levels of newborn neurons. Whether the neurogenic niche can be reactivated and whether SAG neurons can regenerate upon damage is unknown. To study the regenerative capacity of the SAG, we established a lesion paradigm using injections into the otic capsule of the right ear. Upon lesion, the number of apoptotic cells increased, and immune cells infiltrated the SAG of the lesioned side. Importantly, the Neurod-positive progenitor cells re-entered the cell cycle displaying a peak in proliferation at 8 days post lesion before they returned to homeostatic levels at 57 days post lesion. In parallel to reactive proliferation, we observed increased neurogenesis from the Neurod-positive progenitor pool. Reactive neurogenesis started at around 4 days post lesion peaking at 8 days post lesion before the neurogenesis rate decreased again to low homeostatic levels at 57 days post lesion. Additionally, administration of the thymidine analog BrdU and, thereby, labeling proliferating cells and their progeny revealed the generation of new sensory neurons within 19 days post lesion. Taken together, we show that the neurogenic niche of the adult zebrafish SAG can indeed be reactivated to re-enter the cell cycle and to increase neurogenesis upon lesion. Studying the underlying genes and pathways in zebrafish will allow comparative studies with mammalian species and might provide valuable insights into developing cures for auditory and vestibular neuropathies.

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“…The capacity for axon regeneration and functional recovery after spinal cord injury is very limited in mammals. In contrast, zebrafish are able to robustly regrow severed axonal connections and recover swimming function, both at larval and adult stages ( Tsata and Wehner, 2021 ). Thus, zebrafish offer a valuable animal model for studying spinal cord injury and regeneration.…”

Section: Before You Beginmentioning

confidence: 99%