Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America.
PLoS One. 2011;6(10):e25841. doi: 10.1371/journal.pone.0025841. Epub 2011 Oct 7.
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.
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.
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.
我们之前的研究表明，两个已鉴定的斑马鱼运动神经元之间的等效性被与作为这些运动神经元轴突的中间靶标的已鉴定肌肉纤维的相互作用所打破。在这里，我们研究了中间靶标和运动神经元之间信号相互作用的分子基础。
我们提供的证据表明，Netrin 1a 是一种中间靶标衍生的信号，导致两个等效的运动神经元采取不同的命运。我们表明，尽管这两个运动神经元表达相同的 Netrin 受体，但它们的轴突对在中间靶标处遇到的 Netrin 1a 反应不同。此外，我们证明，当 Netrin 1a 被敲低时，表达其他 Netrins 的更远端的中间靶标也可以打破这些运动神经元之间的等效性。
我们的结果表明中间靶标在打破神经元等效性方面具有新的作用。我们呈现的数据表明，在轴突寻径过程中遇到的信号可以使等效神经元采取不同的命运。这些信号可能是使神经元群体多样化并导致正确的电路形成的关键。
