Converting Dendrites to Axons

Abstract

One question in developmental neurobiology is how does, in most cases, only one of the many neurites become the axon for the neuron with the rest of the processes becoming dendrites. Hallam et al. used a green fluorescent protein fusion protein with synaptobrevin to label presynaptic nerve terminals of ventral motor cord neurons and screened Caenorhabditis elegans mutants to identify genes involved in axon specification (see the Perspective by Whited and Garrity). They found that mutants of the syd-1 gene resulted in decreased innervation to the ventral body muscles. The ventral motor neurons come in two types, DD and VD, with VD neurons arising during the larval stages and innervating the ventral muscles and DD neurons arising during embryogenesis and innervating the dorsal muscles. Morphological and colocalization studies with axonal markers suggested that, in syd-1 mutants, the VD neurons formed presynaptic specializations on both the dorsal and ventral processes, instead of being limited to the ventral processes. DD neurons at larval stages in syd-1 mutants showed polarity defects, but in the adult these defects were resolved. Neuronal process specification was also abnormal in another neuron, the ASI chemosensory neurons, in syd-1 mutant worms. Cloning of the syd-1 gene revealed that the protein has several domains: a PDZ protein interaction domain, a C2 domain, and a guanosine triphosphatase-activating (GAP) domain. The authors note that the GAP domain lacks conservation of key residues required for activity toward Rho, and activity toward Rho and Rac is not detectable. Thus, a new player in specifying the presynaptic specialization and the formation of axons has been identified, but SYD-1's exact role remains to be determined. S. J. Hallam, A. Goncharov, J. McEwen, R. Baran, Y. Jin, SYD-1 a presynaptic protein with PDZ, C2 and rhoGAP-like domains, specifies axon identity in C. elegans . Nature Neurosci. 5 , 1137-1146 (2002). [Online Journal] J. L. Whited, P. A. Garrity, Specifying axon identity with Syd-1. Nature Neurosci. 5 , 1107-1108 (2002). [Online Journal]