Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA.
Dev Biol. 2010 Jun 15;342(2):121-33. doi: 10.1016/j.ydbio.2010.03.012. Epub 2010 Mar 24.
Activins are members of the TGF-ss superfamily of secreted growth factors that control a diverse array of processes in vertebrates including endocrine function, cell proliferation, differentiation, immune response and wound repair. In Drosophila, the Activin ligand Dawdle (Daw) has been shown to regulate several aspects of neuronal development such as embryonic axonal pathfinding, neuroblast proliferation in the larval brain and growth cone motility in the visual system. Here we identify a novel role for Activin signaling in regulating synaptic growth at the larval neuromuscular junction (NMJ). Mutants for Daw, the Activin type I receptor Baboon (Babo), and the signal transducer dSmad2, display reduced NMJ size suggesting that Daw utilizes a canonical Activin signal-transduction pathway in this context. Additionally, loss of Daw/Babo activity affects microtubule stability, axonal transport and distribution of Futsch, the Drosophila microtubule associated protein 1B (MAP1B) homolog. We find that Babo signaling is required postsynaptically in the muscle, in contrast to the well-characterized retrograde BMP/Gbb signal that is required for synaptic growth and function in presynaptic cells. Finally, we show that the Daw/Babo pathway acts upstream of gbb, and is involved in maintenance of muscle gbb expression, suggesting that Activins regulate NMJ growth by modulating BMP activity through transcriptional regulation of ligand expression.
激活素是转化生长因子-β（TGF-β）超家族成员中的一种分泌生长因子，它在脊椎动物中控制着一系列不同的过程，包括内分泌功能、细胞增殖、分化、免疫反应和伤口修复。在果蝇中，激活素配体 Dawdle（Daw）已被证明可以调节神经元发育的几个方面，如胚胎轴突寻路、幼虫大脑中的神经母细胞增殖以及视觉系统中的生长锥运动。在这里，我们发现激活素信号在调节幼虫神经肌肉接点（NMJ）的突触生长方面具有新的作用。Daw、激活素 I 型受体 Baboon（Babo）和信号转导蛋白 dSmad2 的突变体显示 NMJ 尺寸减小，这表明 Daw 在这种情况下利用了经典的激活素信号转导途径。此外，Daw/Babo 活性的丧失会影响微管稳定性、轴突运输和 Futsch 的分布，Futsch 是果蝇微管相关蛋白 1B（MAP1B）的同源物。我们发现，Babo 信号在肌肉中的后突触处是必需的，与先前在突触前细胞中对突触生长和功能必需的特征明确的逆行 BMP/Gbb 信号相反。最后，我们表明 Daw/Babo 途径在 gbb 的上游起作用，并参与肌肉 gbb 表达的维持，这表明激活素通过转录调节配体表达来调节 BMP 活性，从而调节 NMJ 生长。
