Axon Regrowth during Development and Regeneration Following Injury Share Molecular Mechanisms

Yaniv, Shiri P.; Issman-Zecharya, Noa; Oren‐Suissa, Meital; Podbilewicz, Benjamin; Schuldiner, Oren

doi:10.1016/j.cub.2012.07.044

Cited by 67 publications

(78 citation statements)

References 35 publications

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“…In late stage pupae, unf accumulates in the Mushroom Body of the brain and in some lateral neurons near the optic lobes. The MB γ-neurons normally undergo pruning and axon regrowth to form adult-specific neural connections via the TOR pathway, but axons fail to regrow following pruning in unf mutants [171]. This function depends on unf/E75 heterodimers and nitric oxide signaling [172].…”

Section: Unf/fax-1/pnr (Nr2e3)mentioning

confidence: 99%

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Bodofsky¹,

Koitz²,

Wightman³

2017

Nuclear Receptor Research

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The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose. Typical nuclear receptors contain two major domains: a DNA-binding domain and a C-terminal domain that may bind a lipophilic hormone. Many of these nuclear receptors play varied roles in animal development, including coordination of life cycle events and cellular differentiation. The well-studied genetic model systems of Drosophila, C. elegans, and mouse permit an evaluation of the extent to which nuclear receptor function in development is conserved or exapted (repurposed) over animal evolution. While there are some specific examples of conserved functions and pathways, there are many clear examples of exaptation. Overall, the evolutionary theme of exaptation appears to be favored over strict functional conservation. Despite strong conservation of DNA-binding domain sequences and activity, the nuclear receptors prove to be highly-flexible regulators of animal development.

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Section: Unf/fax-1/pnr (Nr2e3)mentioning

confidence: 99%

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Bodofsky¹,

Koitz²,

Wightman³

2017

Nuclear Receptor Research

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“…The process of regeneration of injured axons in vertebrates and invertebrates often involves degeneration of the distal part followed by regrowth (Chisholm et al, 2016;Park et al, 2008;Ruschel et al, 2015;Taylor et al, 2005;Yaniv et al, 2012). However, different invertebrates, including nematodes and crustaceans, use plasma membrane fusion as an alternative mechanism for repair of injured axons Hoy et al, 1967;Neumann et al, 2011Neumann et al, , 2015.…”

Section: Introductionmentioning

confidence: 99%

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

2017

Self Cite

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The aging brain undergoes structural changes that affect brain homeostasis, neuronal function and consequently cognition. The complex architecture of dendritic arbors poses a challenge to understanding age-dependent morphological alterations, behavioral plasticity and remodeling following brain injury. Here, we use the PVD polymodal neurons of C. elegans as a model to study how aging affects neuronal plasticity. Using confocal live imaging of C. elegans PVD neurons, we demonstrate age-related progressive morphological alterations of intricate dendritic arbors. We show that mutations in daf-2, which encodes an insulin-like growth factor receptor ortholog, fail to inhibit the progressive morphological aging of dendrites and do not prevent the minor decline in response to harsh touch during aging. We uncovered that PVD aging is characterized by a major decline in the regenerative potential of dendrites following experimental laser dendrotomy. Furthermore, the remodeling of transected dendritic trees by AFF-1-mediated self-fusion can be restored in old animals by daf-2 mutations, and can be differentially re-established by ectopic expression of the fusion protein AFF-1. Thus, ectopic expression of the fusogen AFF-1 in the PVD and mutations in daf-2 differentially rejuvenate some aspects of dendritic regeneration following injury.

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“…Although not injury-triggered, such developmental remodeling may share mechanistic similarities with regeneration, and indeed the C. elegans UNF ortholog fax-1 is required for axon regeneration in chemosensory neurons (Yaniv et al 2012).…”

Section: Axonal Injury and Gene Expressionmentioning

confidence: 99%

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Chisholm¹,

Hutter

Jin

et al. 2016

Genetics

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The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects. Genetic analysis of these pathways has revealed the complex and combinatorial nature of guidance cues, and has delineated how cues guide growth cones via receptor activity and cytoskeletal rearrangement. Several axon guidance pathways also affect directed migrations of non-neuronal cells in C. elegans, with implications for normal and pathological cell migrations in situations such as tumor metastasis. The small number of neurons and highly stereotyped axonal architecture of the C. elegans nervous system allow analysis of axon guidance at the level of single identified axons, and permit in vivo tests of prevailing models of axon guidance. C. elegans axons also have a robust capacity to undergo regenerative regrowth after precise laser injury (axotomy). Although such axon regrowth shares some similarities with developmental axon outgrowth, screens for regrowth mutants have revealed regenerationspecific pathways and factors that were not identified in developmental screens. Several areas remain poorly understood, including how major axon tracts are formed in the embryo, and the function of axon regeneration in the natural environment. KEYWORDS netrin; semaphorin; ephrin; Wnt; Slit; Robo; fasciculation; DLK; growth cone; actin; microtubule; WormBook

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Axon Regrowth during Development and Regeneration Following Injury Share Molecular Mechanisms

Cited by 67 publications

References 35 publications

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

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