Novel genes controlling ventral cord asymmetry and navigation of pioneer axons in C. elegans

Hutter, Harald; Wacker, Irene; Schmid, Christina; Hedgecock, Edward M.

doi:10.1016/j.ydbio.2005.05.025

Cited by 15 publications

(10 citation statements)

References 44 publications

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“…In C. elegans, most circuits in the nervous system are established during embryonic development and additional neurons are added during postembryonic development. Previous studies of axon pathfinding in C. elegans have focused on development of the ventral nerve cord (Durbin 1987;Wightman et al 1997;Hutter et al 2005), sensory neurons of the head (Zallen et al 1999), pharyngeal neurons (Morck et al 2003), and dorsoventral motor and sensory neuron commissures (Hedgecock et al 1985(Hedgecock et al , 1990McIntire 1 et al 1992;. Here we report the results of an investigation of postembryonic axon pathfinding by a set of sensory neurons in the male tail.…”

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confidence: 65%

Genes That Control Ray Sensory Neuron Axon Development in the Caenorhabditis elegans Male

Liu

Emmons

2006

Genetics

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We have studied how a set of male-specific sensory neurons in Caenorhabditis elegans establish axonal connections during postembryonic development. In the adult male, 9 bilateral pairs of ray sensory neurons innervate an acellular fan that serves as a presumptive tactile and olfactory organ during copulation. We visualized ray axon commissures with a ray neuron-specific reporter gene and studied both known and new mutations that affect the establishment of connections to the pre-anal ganglion. We found that the UNC-6/netrin-UNC-40/DCC pathway provides the primary dorsoventral guidance cue to ray axon growth cones. Some axon growth cones also respond to an anteroposterior cue, following a segmented pathway, and most or all also have a tendency to fasciculate. Two newly identified genes, rax-1 and rax-4, are highly specific to the ray neurons and appear to be required for ray axon growth cones to respond to the dorsoventral cue. Among other genes we identified, rax-2 and rax-3 affect anteroposterior signaling or fate specification and rax-5 and rax-6 affect ray identities. We identified a mutation in sax-2 and show that the sax-2/Furry and sax-1/Tricornered pathway affects ectopic neurite outgrowth and establishment of normal axon synapses. Finally, we identified mutations in genes for muscle proteins that affect axon pathways by distorting the conformation of the body wall. Thus ray axon pathfinding relies on a variety of general and more ray neuron-specific genes and provides a potentially fruitful system for further studies of how migrating axon growth cones locate their targets. This system is applicable to the study of mechanisms underlying topographic mapping of sensory neurons into target circuitry where the next stage of information processing is carried out.

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confidence: 65%

Genes That Control Ray Sensory Neuron Axon Development in the Caenorhabditis elegans Male

Liu

Emmons

2006

Genetics

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“…The PVQ axons extend along the ventral nerve cord, following pioneer axons [96]. PVQ axons are in contact with the extracellular matrix and in close proximity to muscles and hypodermis (skin).…”

Section: Discussionmentioning

confidence: 99%

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

et al. 2017

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The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.

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“…In an EMS screen for axon guidance defects in command interneurons of C. elegans, we isolated the allele fmi-1(rh308) (Hutter et al, 2005). We mapped the allele to a 1.8 Mb region on chromosome V between the SNPs R11D1[1] and pKP5086.…”

Section: Mapping and Gene Identificationmentioning

confidence: 99%

“…In the absence of the PVPR axon, the PVQL axon joins the right VNC track, suggesting that the PVQL axon alone is unable to pioneer the left axon track (R. M. Durbin, PhD Thesis, University of Cambridge, 1987). Furthermore, defects in PVPR pioneer axon navigation lead to identical PVQL follower navigation defects, suggesting a strong link between pioneer and follower axons (Hutter, 2003;Hutter et al, 2005). Similarly HSN axons, which extend postembryonically, rely on the presence of either the PVP or PVQ axons for correct navigation (Garriga et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons inC. elegans

et al. 2010

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SUMMARYDevelopment of a functional neuronal network during embryogenesis begins with pioneer axons creating a scaffold along which later-outgrowing axons extend. The molecular mechanism used by these follower axons to navigate along pre-existing axons remains poorly understood. We isolated loss-of-function alleles of fmi-1, which caused strong axon navigation defects of pioneer and follower axons in the ventral nerve cord (VNC) of C. elegans. Notably follower axons, which exclusively depend on pioneer axons for correct navigation, frequently separated from the pioneer. fmi-1 is the sole C. elegans ortholog of Drosophila flamingo and vertebrate Celsr genes, and this phenotype defines a new role for this important molecule in follower axon navigation. FMI-1 has a unique and strikingly conserved structure with cadherin and C-terminal G-protein coupled receptor domains and could mediate cell-cell adhesion and signaling functions. We found that follower axon navigation depended on the extracellular but not on the intracellular domain, suggesting that FMI-1 mediates primarily adhesion between pioneer and follower axons. By contrast, pioneer axon navigation required the intracellular domain, suggesting that FMI-1 acts as receptor transducing a signal in this case. Our findings indicate that FMI-1 is a cell-type dependent axon guidance factor with different domain requirements for its different functions in pioneers and followers.

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Novel genes controlling ventral cord asymmetry and navigation of pioneer axons in C. elegans

Cited by 15 publications

References 44 publications

Genes That Control Ray Sensory Neuron Axon Development in the Caenorhabditis elegans Male

Genes That Control Ray Sensory Neuron Axon Development in the Caenorhabditis elegans Male

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons inC. elegans

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