Academic journal article Genetics

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

Academic journal article Genetics

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

Article excerpt

ABSTRACT

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.

FORMATION of a functional nervous system requires that neurons generate appropriate circuits. Axon pathfinding, the mechanism by which neurons extend processes through the body to the region where they can locate and synapse with their targets, represents an important first step in circuit formation. Over the past decade, several families of attractive and repulsive guidance cues have been identified in Caenorhabditis elegans, Drosophila, and vertebrates, including the UNC-6/Netrins, Slits, Ephrins, and Semaphorins. Specific receptors on the growth cones of developing axons recognize these cues and transduce signals that ultimately lead to changes in the direction of axonal growth (reviewed by TESSIER-LAVIGNE and GOODMAN 1996; MUELLER 1999; DICKSON 2002). Many cell adhesion molecules of the immunoglobulin superfamily are also key players in the control of axonal growth and guidance (ROUGON and HOBERT 2003). Recent studies reveal that secreted cell-signaling molecules best known for their roles as morphogens in controlling cell fate and early embryonic patterning can also act as axon guidance molecules, including Shh, BMP, and Wnts (BUTLER and DODD 2003; CHARRON et al. 2003; LYUKSYUTOVA et al. 2003; YOSHIKAWA et al. 2003). In addition to these broadly acting factors, axon guidance also involves cell-specific factors. For instance, odorant receptors provide the core determinant of identity for axons of olfactory sensory neurons to coalesce into glomeruli in the olfactory bulb (FEINSTEIN et al. 2004). Localized cytosolic Ca2+signals can control the direction of Ca2+ -dependent growth cone turning, which requires a calcium-calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) phosphatase switch (WEN et al. 2004) and depends on myelin-associated glycoprotein (HENLEY et al. 2004).

We have analyzed axon pathfinding by a set of male sensory neurons in C. elegans to determine what general and cell-specific functions guide these axons to their target region. 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. …

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