a developmental timing switch promotes axon outgrowth independent of known guidance receptors发展独立的定时开关促进轴突结果指导受体.pdfVIP

A Developmental Timing Switch Promotes Axon Outgrowth Independent of Known Guidance Receptors Katherine Olsson-Carter, Frank J. Slack* Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, United States of America Abstract To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs) extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4–overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation—the transcriptional regulator LIN-14 and the ‘‘stemness’’ factor LIN-28—and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation. Citation: Olsson-Carter K, Slack FJ (2010) A Developmental Timing Switch Promotes Axon Outgrowth Independent of Known Guidance Receptors. PLoS Genet 6(8): e1001054. doi:10.1371/journal.pgen.1001054 Editor: Stuart K. Kim, Stanford University Medical Center, United States of America Received April 7, 2010; Accepted July 7, 2010; Published August 5, 2010 Copyright: 2010 Olsson-Carter, Slack. This is an open-access article distributed under the terms of the Creative Commons Attribution