PUBLICATION
Transforming growth factor-beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish
- Authors
- Arena, K.A., Zhu, Y., Kucenas, S.
- ID
- ZDB-PUB-220527-8
- Date
- 2022
- Source
- Glia 70(10): 1826-1849 (Journal)
- Registered Authors
- Arena, Kim, Kucenas, Sarah, Zhu, Yunlu
- Keywords
- TGFβ, motor nerve, perineurial glia, regeneration, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Axons/physiology
- Nerve Regeneration/physiology
- Neuroglia/metabolism
- Peripheral Nerve Injuries*/metabolism
- Peripheral Nerves/metabolism
- Signal Transduction
- Transforming Growth Factor beta/metabolism
- Transforming Growth Factors/metabolism
- Zebrafish*
- PubMed
- 35616185 Full text @ Glia
Citation
Arena, K.A., Zhu, Y., Kucenas, S. (2022) Transforming growth factor-beta signaling modulates perineurial glial bridging following peripheral spinal motor nerve injury in zebrafish. Glia. 70(10):1826-1849.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping