UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin.
BACKGROUND
Axon migrations are guided by extracellular cues that can act as repellants or attractants. However, the logic underlying the manner through which attractive and repulsive responses are determined is unclear. Many extracellular guidance cues, and the cellular components that mediate their signals, have been implicated in both types of responses.


RESULTS
Genetic analyses indicate that MIG-10/RIAM/lamellipodin, a cytoplasmic adaptor protein, functions downstream of the attractive guidance cue UNC-6/netrin and the repulsive guidance cue SLT-1/slit to direct the ventral migration of the AVM and PVM axons in C. elegans. Furthermore, overexpression of MIG-10 in the absence of UNC-6 and SLT-1 induces a multipolar phenotype with undirected outgrowths. Addition of either UNC-6 or SLT-1 causes the neurons to become monopolar. Moreover, the ability of UNC-6 or SLT-1 to direct the axon ventrally is enhanced by the MIG-10 overexpression. We also demonstrate that an interaction between MIG-10 and UNC-34, a protein that promotes actin-filament extension, is important in the response to guidance cues and that MIG-10 colocalizes with actin in cultured cells, where it can induce the formation of lamellipodia.


CONCLUSIONS
We conclude that MIG-10 mediates the guidance of AVM and PVM axons in response to the extracellular UNC-6 and SLT-1 guidance cues. The attractive and repulsive guidance cues orient MIG-10-dependant axon outgrowth to cause a directional response.
Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. quinncc@umdnj.edu
Christopher C
CC
Quinn
Douglas S
DS
Pfeil
Esteban
E
Chen
Elizabeth L
EL
Stovall
Maegan V
MV
Harden
Megan K
MK
Gavin
Wayne C
WC
Forrester
Elizabeth F
EF
Ryder
Martha C
MC
Soto
William G
WG
Wadsworth
D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009420:Nervous System / Q000254:growth & development; D000075385:Netrins
D029742:Caenorhabditis elegans Proteins; D036341:Intercellular Signaling Peptides and Proteins; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; D000075385:Netrins; C078146:UNC-6 protein, C elegans; C492285:slt-1 protein, C elegans