Mechanisms of neurite repair

Liu, Han-Hsuan; Jan, Yuh-Nung

doi:10.1016/j.conb.2020.02.010

Cited by 11 publications

(11 citation statements)

References 46 publications

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“…Future improvements for better temporal control could make use of either a pharmacologically controlled gene switch system or the temperature-sensitive GAL80 repressor (Gal80ts) (Nicholson et al, 2008; Zeidler et al, 2004). Whereas we focused on cell autonomous factors in this study, we recognized there are likely non-cell autonomous contributions from epidermal cells and glial cells (DeVault et al, 2018; Liu and Jan, 2020; Song et al, 2012; Yadav et al, 2019; Yin et al, 2021). Future studies of dendrite degeneration at different stages of development as well as adulthood may shed light on strategies to prevent neurodegeneration, to diagnose neurodegeneration early, and to develop drugs promoting neural recovery from injury and diseases.…”

Section: Discussionmentioning

confidence: 99%

Section: Possible Improvements Of the New Modelmentioning

confidence: 99%

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A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster

Liu

Hsu²,

Jan

2021

Preprint

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Neurodegeneration arising from aging, injury or disease has devastating health consequences. Whereas neuronal survival and axon degeneration have been studied extensively, much less is known about how neurodegeneration impacts dendrites. To develop an assay for dendrite degeneration and repair in the Drosophila peripheral nervous system, we used photo-switchable caspase-3 (caspase-LOV) to induce neuronal damage with tunable severity by adjusting illumination duration, thereby revealing cell type-specific responses to caspase-3 induced dendrite degeneration in dendrite arborization (da) neurons. To ask whether mechanisms underlying axon degeneration also govern dendrite degeneration, we tested the involvement of the Wallerian degeneration pathway by examining the effects of expressing the mouse Wallerian degeneration slow (WldS) protein and knockdown of the Drosophila sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein (dSarm1) and Axundead (Axed) in class 4 da neurons. Here we report WldS expression or knockdown of dSarm1 improved dendrite repair following caspase-3 induced dendrite degeneration. Whereas both dSarm1 and Axed were required for thermal nocifensive behavior in uninjured animals, WldS expression improved the recovery of thermal nocifensive behavior that was impaired by chronic low-level of caspase-LOV activity. By establishing ways to induce graded dendrite degeneration, we uncover a protective role of WldS in caspase-3 induced dendrite degeneration and repair.

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Section: Discussionmentioning

confidence: 99%

Section: Possible Improvements Of the New Modelmentioning

confidence: 99%

A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster

Liu

Hsu²,

Jan

2021

Preprint

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“…In the forebrain, excitatory neurons have pyramidally shaped cell bodies (somata) with axonal and apicobasal dendritic processes, which originate from the apex and base of their pyramidal shapes (Mohan, et al, 2015; Spruston, 2008). Understanding how pyramidal neurons generate and maintain their specialized morphology is imperative for tackling neurodevelopmental and neurodegenerative disorders, and devising neuroregenerative strategies (Liu and Jan, 2020; Prem, et al, 2020; Copf, 2016; Kulkarni and Firestein, 2012).…”

Section: Introductionmentioning

confidence: 99%

Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation

Radler

Liu

Peng

et al. 2022

Preprint

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Pyramidal neurons are the major cell type of the forebrain, consisting of a pyramidally shaped soma with axonal and apicobasal dendritic processes. It is poorly understood how the neuronal soma morphs from a sphere to pyramid, while generating neurites of the proper shape and orientation. Here, we discovered that the spherical somata of immature neurite-less neurons possess a circumferential wreath-like network of septin filaments, which promotes myosin II localization and suppresses Arp2/3 activity at the base of filopodial actin bundles. The septin network facilitates neurite formation by stabilizing nascent filopodia, which mature to neurites, and concomitantly maintains a consolidated soma by suppressing the extension of lamellipodia. We show that this septin function is critical for the morphogenesis and spatial orientation of pyramidal somata and their neurites in vitro and in vivo. Therefore, the somatic septin cytoskeleton provides a key morphogenetic mechanism for neuritogenesis and the development of pyramidal neurons.

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“…DRG neurons are a useful model to study mechanisms regulating the neuronal regeneration program following axotomy. Injury to peripheral axonal branches induces transcription-dependent changes of regeneration-associated genes and proteins, enhancing the regeneration potential of DRG neurons and thus promoting regeneration of the damaged axons [ 1 , 2 ]. This conditioning lesion of peripheral axons also allows regeneration of central axonal branches, but prior injury to these branches is insufficient to activate the same neuronal regeneration program [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion

Dubový

Hradilová-Svíženská

Brázda

et al. 2021

IJMS

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One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)—the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury.

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Mechanisms of neurite repair

Cited by 11 publications

References 46 publications

A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster

A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster

Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation

Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion

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