Models of axon regeneration in Drosophila

Brace, E. J.; DiAntonio, Aaron

doi:10.1016/j.expneurol.2016.03.014

Cited by 29 publications

(23 citation statements)

References 73 publications

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“…These studies are revealing evolutionary conserved molecular mechanisms. Nmnat is involved in maintaining axonal integrity (Fang and Bonini, ; Soares et al, ), and the DLK‐JNK and PTEN‐Akt signaling pathways can promote axonal re‐growth (Song et al, ; Brace and Diantonio, ). The involvement of glial cells in axonal regeneration has been little investigated.…”

Section: Drosophila Comes Of Age As a Model Organism To Investigate Rmentioning

confidence: 99%

Gene network underlying the glial regenerative response to central nervous system injury

Kato

Losada‐Pérez

Hidalgo

2017

Developmental Dynamics

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Although the central nervous system does not regenerate, injury induces repair and regenerative responses in glial cells. In mammals, activated microglia clear up apoptotic cells and debris resulting from the injury, astrocytes form a scar that contains the lesion, and NG2-glia elicit a prominent regenerative response. NG2-glia regenerate themselves and differentiate into oligodendrocytes, which remyelinate axons leading to some recovery of locomotion. The regenerative response of glial cells is evolutionarily conserved across the animals and Drosophila genetics revealed an underlying gene network. This involves the genes Notch, kon-tiki, eiger, dorsal, and prospero, homologues of mammalian Notch1, ng2, TNF, NFjB, and prox1, respectively. Feedback loops between these genes enable a surge in proliferation in response to injury and ensuing differentiation. Negative feedback sets a timer for proliferation, and prevents uncontrolled growth that could lead to glioma. Remarkable parallels are found in these genetic relationships between fruit flies and mammals. Drosophila findings provide insights into gene functions that could be manipulated in stem cells and progenitors for therapeutic repair. Developmental Dynamics 247:85-93, 2018. V C 2017 Wiley Periodicals, Inc.

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Section: Drosophila Comes Of Age As a Model Organism To Investigate Rmentioning

confidence: 99%

Gene network underlying the glial regenerative response to central nervous system injury

Kato

Losada‐Pérez

Hidalgo

2017

Developmental Dynamics

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“…To study dendrite recovery from injury, we needed to enable animals to survive multiple imaging sessions and fully recover. Whereas it is possible to repeatedly image the wings of intact adults to study the regeneration of axons of wing neurons after injury (Soares et al 2014;Brace and DiAntonio 2017), those wing neurons are unsuitable for examining dendrite architecture because they lack complex dendritic arbors.…”

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confidence: 99%

Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix metalloproteinase 2

DeVault

Izabel

et al. 2018

Genes Dev.

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Dendrites possess distinct structural and functional properties that enable neurons to receive information from the environment as well as other neurons. Despite their key role in neuronal function, current understanding of the ability of neurons to regenerate dendrites is lacking. This study characterizes the structural and functional capacity for dendrite regeneration in vivo in adult animals and examines the effect of neuronal maturation on dendrite regeneration. We focused on the class IV dendritic arborization (c4da) neuron of the sensory system, which has a dendritic arbor that undergoes dramatic remodeling during the first 3 d of adult life and then maintains a relatively stable morphology thereafter. Using a laser severing paradigm, we monitored regeneration after acute and spatially restricted injury. We found that the capacity for regeneration was present in adult neurons but diminished as the animal aged. Regenerated dendrites recovered receptive function. Furthermore, we found that the regenerated dendrites show preferential alignment with the extracellular matrix (ECM). Finally, inhibition of ECM degradation by inhibition of matrix metalloproteinase 2 (Mmp2) to preserve the extracellular environment characteristics of young adults led to increased dendrite regeneration. These results demonstrate that dendrites retain regenerative potential throughout adulthood and that regenerative capacity decreases with aging.

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“…In the PNS, the JNK signalling pathway is activated in response to axon injury in damaged neurons, where it regulates injury-induced transcriptional changes (Xiong et al, 2010). The activation of this signalling pathway in the damaged neuron can promote axonal re-growth (Brace and DiAntonio, 2017;Song et al, 2012). In addition, it has been shown that axon self-destruction leads to the activation of Draper/Ced-1/MEGF-10.…”

Section: Activation Of Jnk Signalling In Glia Cells Is Necessary But mentioning

confidence: 99%

Dpp and Hedgehog promote the Glial response to neuronal damage in the developing Drosophila Visual system

Velarde

Quevedo

Estella

et al. 2020

Preprint

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Damage in the nervous system induces a stereotypical response that is mediated by glial cells. Here, we use the eye disc to explore the mechanisms involved in promoting glial cell response after neural injuries. We demonstrate that eye glia cells rapidly respond to neuronal injury by increasing in number and undergoing morphological changes, which grant them phagocytic abilities.We found that this glial response is controlled by the activity of the long-range signalling pathways, decapentaplegic (dpp) and hedgehog (hh). These pathways are activated in the damaged region and their functions are necessary for inducing glial cell proliferation and migration to the eye discs. The latter of these two processes depends on the function of the JNK pathway, which is cooperatively activated by dpp and hh signalling.3

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Models of axon regeneration in Drosophila

Cited by 29 publications

References 73 publications

Gene network underlying the glial regenerative response to central nervous system injury

Gene network underlying the glial regenerative response to central nervous system injury

Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix metalloproteinase 2

Dpp and Hedgehog promote the Glial response to neuronal damage in the developing Drosophila Visual system

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