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Abstract
Neurons innervate multiple targets by sprouting axon branches from a primary axon
shaft. We show here that the ventral guidance factor unc-6 (Netrin), its receptor
unc-40 (DCC), and the gene madd-2 stimulate ventral axon branching in C. elegans chemosensory
and mechanosensory neurons. madd-2 also promotes attractive axon guidance to UNC-6
and assists unc-6- and unc-40-dependent ventral recruitment of the actin regulator
MIG-10 in nascent axons. MADD-2 is a tripartite motif protein related to MID-1, the
causative gene for the human developmental disorder Opitz syndrome. MADD-2 and UNC-40
proteins preferentially localize to a ventral axon branch that requires their function;
genetic results indicate that MADD-2 potentiates UNC-40 activity. Our results identify
MADD-2 as an UNC-40 cofactor in axon attraction and branching, paralleling the role
of UNC-5 in repulsion, and provide evidence that targeting of a guidance factor to
specific axonal branches can confer differential responsiveness to guidance cues.
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