The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Abstract

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

Axonal Transport Of An Insulin-Like Peptide Mrna Promotes Stress Recovery InC. Elegans

“…Axonal translation is important in axon migration and synaptogenesis (Holt and Schuman, 2013). In C. elegans, synapse formation along the length of axons and axon outgrowth continue during larval stages [(Gujar et al, 2017;Lipton et al, 2018;Shen and Bargmann, 2003;White et al, 1978;White et al, 1986;Zhao and Nonet, 2000); reviewed in (Chisholm et al, 2016)]. These might require axonal Golgi to package the necessary proteins in larvae (Colón-Ramos et al, 2007;Shen and Bargmann, 2003).…”

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

“…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.…”

Intrinsic mechanisms of neuronal axon regeneration

“…Other aspects of axon regeneration, which include the roles of the cellular environment, axon–soma signalling and growth cone formation and dynamics have been extensively covered in recent reviews 4,5,8,10–13 and will not be discussed here. This Review largely focuses on studies on mice, as recent reviews have covered axon regeneration in other model systems including C. elegans 14,15 , Drosophila melanogaster 16 and fish 17 .…”