A Statistically-Oriented Asymmetric Localization (SOAL) Model for Neuronal Outgrowth Patterning by Caenorhabditis elegans UNC-5 (UNC5) and UNC-40 (DCC) Netrin Receptors

摘要

Neurons extend processes that vary in number, length, and direction of “outgrowth”. Extracellular cues help determine outgrowth patterns. In Caenorhabditis elegans, neurons respond to the extracellular (netrin) cue via (DCC) and (UNC5) receptors. Previously, we presented evidence that asymmetric localization at the plasma membrane is self-organizing, and that can localize and mediate outgrowth at randomly selected sites. Here, we provide further evidence for a statistically-oriented asymmetric localization (SOAL) model in which receptor activity affects patterns of axon outgrowth by regulating asymmetric localization. According to the SOAL model, the direction of outgrowth activity fluctuates across the membrane over time. Random walk modeling predicts that increasing the degree to which the direction of outgrowth fluctuates will decrease the outward displacement of the membrane. By differentially affecting the degree to which the direction of outgrowth activity fluctuates over time, extracellular cues can produce different rates of outgrowth along the surface and create patterns of “extension”. Consistent with the SOAL model, we show that mutations alter asymmetric localization, increase the degree to which the direction of outgrowth fluctuates, and reduce the extent of outgrowth in multiple directions relative to the source of . These results are inconsistent with current models, which predict that mediates a “repulsive” response to . Genetic interactions suggest that acts through the (NAV2) cytoplasmic protein to regulate asymmetric localization in response to both the and href="http://www.wormbase.org/db/get?name=WBGene00001188;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=5753861&issue-id=304079&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">EGL-20 (Wnt) extracellular cues.