Hernandez-Fleming Melissa, Rohrbach Ethan W, Bashaw Greg J
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Cell Rep. 2017 Jan 3;18(1):174-184. doi: 10.1016/j.celrep.2016.12.027.
Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin. In contrast to other examples of reverse signaling where Sema1a triggers repulsion through activation of Rho in response to Plexin binding, in commissural neurons Sema-1a acts independently of Plexins to inhibit Rho to promote attraction to the midline. These findings suggest that Sema-1a reverse signaling can elicit distinct axonal responses depending on differential engagement of distinct ligands and signaling effectors.
连合轴突必须穿过中线以形成功能性的中线回路。在无脊椎动物的神经索和脊椎动物的脊髓中，中线交叉部分是由Netrin依赖性化学吸引介导的。然而，在Netrin或其受体Frazzled/DCC的突变体中，交叉的缺失并不完全，这表明存在其他途径。我们确定跨膜信号素Sema-1a是果蝇中枢神经系统中中线交叉的重要调节因子。我们表明，响应分泌的信号素Sema-2a和Sema-2b，Sema-1a作为受体发挥作用，独立于Netrin促进交叉。与其他反向信号传导的例子不同，在那些例子中Sema1a通过响应丛状蛋白结合激活Rho来触发排斥，在连合神经元中，Sema-1a独立于丛状蛋白发挥作用，抑制Rho以促进对中线的吸引。这些发现表明，Sema-1a反向信号传导可以根据不同配体和信号效应器的不同参与引发不同的轴突反应。
