netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targetsnetrin信号中断两个识别斑马鱼运动神经元之间的等价揭示中间目标的一个新的角色.pdfVIP

Netrin Signaling Breaks the Equivalence between Two Identified Zebrafish Motoneurons Revealing a New Role of Intermediate Targets Laura A. Hale, Daniel K. Fowler, Judith S. Eisen* Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America Abstract Background: We previously showed that equivalence between two identified zebrafish motoneurons is broken by interactions with identified muscle fibers that act as an intermediate target for the axons of these motoneurons. Here we investigate the molecular basis of the signaling interaction between the intermediate target and the motoneurons. Principal Findings: We provide evidence that Netrin 1a is an intermediate target-derived signal that causes two equivalent motoneurons to adopt distinct fates. We show that although these two motoneurons express the same Netrin receptors, their axons respond differently to Netrin 1a encountered at the intermediate target. Furthermore, we demonstrate that when Netrin 1a is knocked down, more distal intermediate targets that express other Netrins can also function to break equivalence between these motoneurons. Significance: Our results suggest a new role for intermediate targets in breaking neuronal equivalence. The data we present reveal that signals encountered during axon pathfinding can cause equivalent neurons to adopt distinct fates. Such signals may be key in diversifying a neuronal population and leading to correct circuit formation. Citation: Hale LA, Fowler DK, Eisen JS (2011) Netrin Signaling Breaks the Equivalence between Two Identified Zebrafish Motoneurons Revealing a New Role of Intermediate Targets. PLoS ONE 6(10): e25841. doi:10.1371/journal.pone.0025841 Editor: Jonathan Matsui, Pomona College, United States of America Received July 14, 2011; Accepted September 12, 2011; Published October 7,