The correct wiring of the nervous system requires that both axons navigate to their targets and maintain their correct position in axon fascicles after termination of axon outgrowth. Previous work in the lab has revealed a novel mechanism that ensures that axons maintain their position in the axonal tracts of the ventral nerve cord (VNC) of C. elegans. The neuron PVT mediates maintenance in the VNC through the temporally controlled secretion of 2-immunoglobulin domain proteins, whose function, at least for ZIG-4, has been shown to be required for axon maintenance (1). In addition,
egl-15, which encodes the fibroblast growth factor receptor, has been implicated in the maintenance of axons at the VNC. A particular isoform,
egl-15(5A) , defined by an extracellular immunoglobin domain, functions in the hypodermis, in a kinase-domain independent-manner, to mediate the maintenance of neighboring axons (2). We have recently discovered that a new gene,
sax-8, is implicated in the maintenance of axon position in the VNC. Mutations in
sax-8 were isolated in a screen for mutants defective in nerve ring morphology, and result in the abnormal maintenance of nerve ring position (3). Our analysis of
sax-8 mutants reveals defects in the maintenance of a number of axons in the VNC. By three-factor mapping with
lon-1 and
unc-36, we mapped
sax-8 to a 1cM region. This region contains the
dig-1 gene, a large secreted extracellular protein (see Abstract by Hull et al.).
sax-8 fails to complement
dig-1 and the mutant phenotype of
sax-8 can be rescued with a cosmid that covers solely
dig-1. Known alleles of
dig-1 also display axon maintenance defects in the VNC. While axon positioning is normal in early
dig-1/sax-8 mutant L1s, they later fail to maintain their proper positioning. Preliminary reporter gene analysis indicates that
dig-1 is expressed in muscle and hypodermis but not in neurons of the ventral nerve cord. We hypothesize that the DIG-1 protein is part of the ECM that ensheathes the VNC fascicles. 1.Aurelio O, Hall D H, Hobert O (2002). Science 295. 2.Bulow H, Boulin T, Hobert O (2004). Neuron, 42. 3.Zallen J, Kirch S, Bargmann C (1999). Development 126.