Axon guidance and injury — lessons from Wnts and Wnt signaling

Onishi, Keisuke; Hollis, Edmund R.; Zou, Yimin

doi:10.1016/j.conb.2014.05.005

Cited by 78 publications

(63 citation statements)

References 54 publications

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“…Axon navigation defects are sometimes found in addition to process outgrowth defects, but limited to an even smaller number of neurons. The role of Wnts in axonal navigation in C. elegans contrasts with the apparently more substantial function of Wnts in a-p navigation of axons in both Drosophila and vertebrates (Yam and Charron 2013;Onishi et al 2014).…”

Section: Tropic Guidance Cuesmentioning

confidence: 88%

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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Section: Tropic Guidance Cuesmentioning

confidence: 88%

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Chisholm¹,

Hutter

Jin

et al. 2016

Genetics

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“…Since our data show that Vangl2 accumulates at developing NMJs and is likely to be expressed in both presynaptic nerve terminals and postsynaptic muscle domains, it is possible that a Vangl2-dependent signaling is activated in motor axons to regulate and stop the growth of axons once they have reached their target. The role of the PCP pathway in Wnt-induced growth of axons has been well documented (Onishi et al, 2014). However, the similarity between Dkk1-and Vangl2-induced phenotypes raises the interesting hypothesis that both Vangl2 and β-catenin signal in the same pathway.…”

Section: Wnt Signaling In Presynaptic Branching and Motor Axon Growthmentioning

confidence: 99%

Wnts contribute to neuromuscular junction formation through distinct signaling pathways

et al. 2017

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Understanding the developmental steps that shape formation of the neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers is crucial. Wnt morphogens are key players in the formation of this specialized peripheral synapse, but their individual and collaborative functions and downstream pathways remain poorly understood at the NMJ. Here, we demonstrate through Wnt4 and Wnt11 gain-of-function studies in cell culture or in mice that Wnts enhance acetylcholine receptor (AChR) clustering and motor axon outgrowth. By contrast, loss of Wnt11 or Wnt-dependent signaling in vivo decreases AChR clustering and motor nerve terminal branching. Both Wnt4 and Wnt11 stimulate AChR mRNA levels and AChR clustering downstream of activation of the β-catenin pathway. Strikingly, Wnt4 and Wnt11 co-immunoprecipitate with Vangl2, a core component of the planar cell polarity (PCP) pathway, which accumulates at embryonic NMJs. Moreover, mice bearing a Vangl2 loss-of-function mutation (loop-tail) exhibit fewer AChR clusters and overgrowth of motor axons bypassing AChR clusters. Together, our results provide genetic and biochemical evidence that Wnt4 and Wnt11 cooperatively contribute to mammalian NMJ formation through activation of both the canonical and Vangl2-dependent core PCP pathways.

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“…1). The mechanisms by which Wnt signaling regulates later CNS developmental processes including corticogenesis (Bielen and Houart, 2014;Inestrosa and Varela-Nallar, 2015;Fortress and Frick, 2016), neural crest emergence (De Calisto et al, 2005;Pegoraro and Monsoro-Burq, 2013;Mayor and Theveneau, 2014), eye morphogenesis (Cavodeassi, 2014;Fujimura, 2016), axon growth and guidance (Guan and Rao, 2003;Clark et al, 2012;Onishi et al, 2014;Petrova et al, 2014), synaptic formation and function (Sanes and Lichtman, 2001;Burden, 2002;Salinas, 2012;Dickins and Salinas, 2013;Poon et al, 2013;Stamatakou and Salinas, 2014), and adult neurogenesis (Bielen and Houart, 2014) have been reviewed extensively elsewhere.…”

Section: Introductionmentioning

confidence: 99%

Wnt/β‐catenin signaling during early vertebrate neural development

Brafman

Willert

2017

Developmental Neurobiology

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The vertebrate central nervous (CNS) is comprised of vast number of distinct cell types arranged in a highly organized manner. This high degree of complexity is achieved by cellular communication, including direct cell-cell contact, cell-matrix interactions, and cell-growth factor signaling. Among the several developmental signals controlling the development of the CNS, Wnt proteins have emerged as particularly critical and, hence, have captivated the attention of many researchers. With Wnts’ evolutionarily conserved function as primordial symmetry breaking signals, these proteins and their downstream effects are responsible for simultaneously establishing cellular diversity and tissue organization. With their expansive repertoire of secreted agonists and antagonists, cell surface receptors, signaling cascades and downstream biological effects, Wnts are ideally suited to control the complex processes underlying vertebrate neural development. In this review, we will describe the mechanisms by which Wnts exert their potent effects on cells and tissues and highlight the many roles of Wnt signaling during neural development, starting from the initial induction of the neural plate, the subsequent patterning along the embryonic axes, to the intricately organized structure of the CNS.

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Axon guidance and injury — lessons from Wnts and Wnt signaling

Cited by 78 publications

References 54 publications

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Wnts contribute to neuromuscular junction formation through distinct signaling pathways

Wnt/β‐catenin signaling during early vertebrate neural development

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