Transforming growth factor‐beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish

Arena, Kimberly A.; Zhu, Yunlu; Kucenas, Sarah

doi:10.1002/glia.24220

Cited by 6 publications

(1 citation statement)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, it has been shown that inhibition of TGF-β signaling perturbs perineurial glia maturation, a cell type that ensheaths axon-Schwann cell bundles and forms the bloodnerve-barrier (Kucenas, 2015;Morris et al, 2017). Interestingly, another study from the same laboratory has shown that TGF-β signaling pathway, through its downstream mediator connective tissue growth factor-a (ctgfa), is involved in forming the bridge between proximal and distal stumps after motor nerve injury in zebrafish embryos (Arena et al, 2022). However, to date, there is no specific evidence demonstrating the role of TGFβ in ALS zebrafish models.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of tgfb1a partially improves ALS phenotype in a transient zebrafish model

Gonzalez,

Cuenca,

Allende

2024

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) corresponds to a neurodegenerative disorder marked by the progressive degeneration of both upper and lower motor neurons located in the brain, brainstem, and spinal cord. ALS can be broadly categorized into two main types: sporadic ALS (sALS), which constitutes approximately 90% of all cases, and familial ALS (fALS), which represents the remaining 10% of cases. Transforming growth factor type-β (TGF-β) is a cytokine involved in various cellular processes and pathological contexts, including inflammation and fibrosis. Elevated levels of TGF-β have been observed in the plasma and cerebrospinal fluid (CSF) of both ALS patients and mouse models. In this perspective, we explore the impact of the TGF-β signaling pathway using a transient zebrafish model for ALS. Our findings reveal that the knockdown of tgfb1a lead to a partial prevention of motor axon abnormalities and locomotor deficits in a transient ALS zebrafish model at 48 h post-fertilization (hpf). In this context, we delve into the proposed distinct roles of TGF-β in the progression of ALS. Indeed, some evidence suggests a dual role for TGF-β in ALS progression. Initially, it seems to exert a neuroprotective effect in the early stages, but paradoxically, it may contribute to disease progression in later stages. Consequently, we suggest that the TGF-β signaling pathway emerges as an attractive therapeutic target for treating ALS. Nevertheless, further research is crucial to comprehensively understand the nuanced role of TGF-β in the pathological context.

show abstract

Section: Discussionmentioning

confidence: 99%

Knockdown of tgfb1a partially improves ALS phenotype in a transient zebrafish model

Gonzalez,

Cuenca,

Allende

2024

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

Transforming growth factor‐beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish

Arena

Zhu

Kucenas

2022

Glia

View full text Add to dashboard Cite

Spinal motor nerves are necessary for organismal locomotion and survival.In zebrafish and most vertebrates, these peripheral nervous system structures are composed of bundles of axons that naturally regenerate following injury. However, the cellular and molecular mechanisms that mediate this process are still only partially understood. Perineurial glia, which form a component of the blood-nerve barrier, are necessary for the earliest regenerative steps by establishing a glial bridge across the injury site as well as phagocytosing debris. Without perineurial glial bridging, regeneration is impaired. In addition to perineurial glia, Schwann cells, the cells that ensheath and myelinate axons within the nerve, are essential for debris clearance and axon guidance. In the absence of Schwann cells, perineurial glia exhibit perturbed bridging, demonstrating that these two cell types communicate during the injury response.While the presence and importance of perineurial glial bridging is known, the molecular mechanisms that underlie this process remain a mystery. Understanding the cellular and molecular interactions that drive perineurial glial bridging is crucial to unlocking the mechanisms underlying successful motor nerve regeneration. Using laser axotomy and in vivo imaging in zebrafish, we show that transforming growth factor-beta (TGFβ) signaling modulates perineurial glial bridging. Further, we identify connective tissue growth factor-a (ctgfa) as a downstream effector of TGF-β signaling that works in a positive feedback loop to mediate perineurial glial bridging. Together, these studies present a new signaling pathway involved in the perineurial glial injury response and further characterize the dynamics of the perineurial glial bridge.

show abstract

Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord

Brown,

Barber,

Kucenas

2024

Glia

View full text Add to dashboard Cite

The central and peripheral nervous systems (CNS and PNS, respectively) exhibit remarkable diversity in the capacity to regenerate following neuronal injury with PNS injuries being much more likely to regenerate than those that occur in the CNS. Glial responses to damage greatly influence the likelihood of regeneration by either promoting or inhibiting axonal regrowth over time. However, despite our understanding of how some glial lineages participate in nerve degeneration and regeneration, less is known about the contributions of peripheral satellite glial cells (SGC) to regeneration failure following central axon branch injury of dorsal root ganglia (DRG) sensory neurons. Here, using in vivo, time‐lapse imaging in larval zebrafish coupled with laser axotomy, we investigate the role of SGCs in axonal regeneration. In our studies we show that SGCs respond to injury by relocating their nuclei to the injury site during the same period that DRG neurons produce new central branch neurites. Laser ablation of SGCs prior to axon injury results in more neurite growth attempts and ultimately a higher rate of successful central axon regrowth, implicating SGCs as inhibitors of regeneration. We also demonstrate that this SGC response is mediated in part by ErbB signaling, as chemical inhibition of this receptor results in reduced SGC motility and enhanced central axon regrowth. These findings provide new insights into SGC‐neuron interactions under injury conditions and how these interactions influence nervous system repair.

show abstract

Transforming growth factor‐beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish

Cited by 6 publications

References 79 publications

Knockdown of tgfb1a partially improves ALS phenotype in a transient zebrafish model

Knockdown of tgfb1a partially improves ALS phenotype in a transient zebrafish model

Transforming growth factor‐beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish

Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord

Contact Info

Product

Resources

About