RT Journal Article SR Electronic T1 UNC-5 (UNC5) Regulates the Length and Number of Processes that Caenorhabditis elegans Neurons Can Develop JF bioRxiv FD Cold Spring Harbor Laboratory SP 083436 DO 10.1101/083436 A1 Gerard Limerick A1 Xia Tang A1 Won Suk Lee A1 Ahmed Mohamed A1 Aseel Al-Aamiri A1 William G. Wadsworth YR 2016 UL http://biorxiv.org/content/early/2016/10/25/083436.abstract 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.