Parker Louise, Ellis Jeremy E, Nguyen Minh Q, Arora Kavita
Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697-2300, USA.
Development. 2006 Dec;133(24):4981-91. doi: 10.1242/dev.02673.
Axon guidance is regulated by intrinsic factors and extrinsic cues provided by other neurons, glia and target muscles. Dawdle (Daw), a divergent TGF-beta superfamily ligand expressed in glia and mesoderm, is required for embryonic motoneuron pathfinding in Drosophila. In daw mutants, ISNb and SNa axons fail to extend completely and are unable to innervate their targets. We find that Daw initiates an activin signaling pathway via the receptors Punt and Baboon (Babo) and the signal-transducer Smad2. Furthermore, mutations in these signaling components display similar axon guidance defects. Cell-autonomous disruption of receptor signaling suggests that Babo is required in motoneurons rather than in muscles or glia. Ectopic ligand expression can rescue the daw phenotype, but has no deleterious effects. Our results indicate that Daw functions in a permissive manner to modulate or enable the growth cone response to other restricted guidance cues, and support a novel role for activin signaling in axon guidance.
轴突导向受其他神经元、神经胶质细胞和靶肌肉提供的内在因素和外在信号的调控。Dawdle（Daw）是一种在神经胶质细胞和中胚层中表达的不同寻常的转化生长因子-β超家族配体，对于果蝇胚胎运动神经元的路径寻找是必需的。在daw突变体中，ISNb和SNa轴突无法完全延伸，并且无法支配它们的靶标。我们发现，Daw通过受体Punt和狒狒（Babo）以及信号转导分子Smad2启动激活素信号通路。此外，这些信号传导成分中的突变表现出相似的轴突导向缺陷。受体信号传导的细胞自主破坏表明，Babo在运动神经元中是必需的，而不是在肌肉或神经胶质细胞中。异位配体表达可以挽救daw表型，但没有有害影响。我们的结果表明，Daw以一种许可的方式发挥作用，以调节或使生长锥对其他受限的导向线索作出反应，并支持激活素信号在轴突导向中的新作用。
