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Program of the 2004 East Coast Worm Meeting - Caenorhabditis ...

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21. mig-10 functions downstream <strong>of</strong> unc-6 and slt-1 to mediate axon guidance.<br />

Christopher C. Quinn 1 , Elizabeth Stovall 2 , Elizabeth F. Ryder 2 , William G. Wadsworth 1<br />

1Dept. <strong>of</strong> Pathology, Robert Wood Johnson Medical School, Piscataway, NJ<br />

2Biology and Biotechnology, Worcester Polytechnic Institutute, Worcester, MA<br />

Migrating axons are guided through <strong>the</strong> developing nervous system by extracellular guidance<br />

cues. These cues interact with transmembrane receptors, causing an attractive or repulsive<br />

response to <strong>the</strong> guidance cue. While many extracellular guidance cues and <strong>the</strong>ir receptors have<br />

been identified, <strong>the</strong> intracellular mechanisms that mediate <strong>the</strong> response to <strong>the</strong> guidance cues are<br />

largely unknown.<br />

The ventral migrations <strong>of</strong> <strong>the</strong> AVM and PVM axons are guided by attraction to netrin/UNC-6<br />

and repulsion from slit/SLT-1 (Gitai et al, 2002, Neuron 37,53-65; C.C.Q, unpublished<br />

observations). We have found that MIG-10 is expressed in <strong>the</strong> AVM and PVM axons where it<br />

functions cell-autonomously to mediate <strong>the</strong> axon’s response to both netrin/UNC-6 and slit/SLT-1.<br />

This function occurs in parallel to UNC-34/enabled, a regulator <strong>of</strong> actin polymerization that acts<br />

downstream <strong>of</strong> netrin/UNC-6 and slit/SLT-1 (Yu et al, 2002, Nat. Neurosci. 5, 1147-1154). MIG-10<br />

is a cytoplasmic protein that includes several proline rich domains as well as a Ras Association<br />

domain and a Plekstrin Homology domain. We propose that MIG-10 serves as a<br />

signaling/adaptor protein that can integrate <strong>the</strong> repulsive and attractive guidance signals received<br />

by <strong>the</strong>se axons.

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