The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

被引:61
作者
Chisholm, Andrew D. [1 ]
Hutter, Harald [3 ]
Jin, Yishi [1 ,2 ,4 ]
Wadsworth, William G. [5 ]
机构
[1] Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
[3] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada
[4] Howard Hughes Med Inst, Dept Pathol & Lab Med, Chevy Chase, MD USA
[5] Rutgers Robert Wood Johnson Med Sch, Dept Pathol, Piscataway, NJ 08854 USA
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院; 美国国家卫生研究院;
关键词
netrin; semaphorin; ephrin; Wnt; Slit; Robo; fasciculation; DLK; growth cone; actin; microtubule; WormBook; HEPARAN-SULFATE PROTEOGLYCANS; SYNAPSE-ASSEMBLY PROTEINS; CONTROLS CELL-MIGRATION; EPHRIN EFN-4 FUNCTIONS; C-ELEGANS; GROWTH CONE; BASEMENT-MEMBRANE; NERVOUS-SYSTEM; IN-VIVO; NEURONAL REGENERATION;
D O I
10.1534/genetics.115.186262
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 regeneration-specific 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.
引用
收藏
页码:849 / 882
页数:34
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