PT  - JOURNAL ARTICLE
AU  - Gerard Limerick
AU  - Xia Tang
AU  - Won Suk Lee
AU  - Ahmed Mohamed
AU  - Aseel Al-Aamiri
AU  - William G. Wadsworth
TI  - UNC-5 (UNC5) Regulates the Length and Number of Processes that <em>Caenorhabditis elegans</em> Neurons Can Develop
AID  - 10.1101/083436
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 083436
4099  - http://biorxiv.org/content/early/2016/10/25/083436.short
4100  - http://biorxiv.org/content/early/2016/10/25/083436.full
AB  - Neurons extend processes that vary in number, length, and direction of outgrowth. Extracellular molecules act as cues to regulate this patterning. In Caenorhabditis elegans, neurons respond to the UNC-6 (netrin) cue via UNC-5 (UNC5) and UNC-40 (DCC) receptors. Here we present evidence that UNC-5 regulates the length and number of processes that neurons develop. Genetic analysis suggests UNC-5 functions with UNC-6 and EGL-20 (wnt), the SAX-3 (Robo) receptor, and the cytoplasmic proteins UNC-53 (NAV2), MIG-15 (NIK kinase), and MADD-2 (TRIM) to regulate the asymmetric localization of UNC-40 to a surface of the neuron. We have postulated that UNC-40 polarization is self-organizing and that the surface to which UNC-40 localizes and mediates outgrowth is stochastically determined. At any instance of time, there is a probability that UNC-40-mediated outgrowth will occur in a specific direction. We find that UNC-5 activity reduces the degree to which the direction of outgrowth fluctuations over time. Random walk modeling predicts that by decreasing the fluctuation UNC-5 activity increases the mean-squared distance that outgrowth movement could covered over a given time. This suggests that UNC-5 activity creates outgrowth patterns by varying the rate of outgrowth along a surface of the neuron.