Division of Neuroanatomy, Innsbruck Medical University, Muellerstrasse 59, A-6020 Innsbruck, Austria.
Hippocampus. 2012 Mar;22(3):434-41. doi: 10.1002/hipo.20910. Epub 2011 Jan 14.
Sprouty proteins act as negative feedback inhibitors of fibroblast growth factor (FGF) signaling. FGFs belong to the neurotrophic factors and are involved in axonal growth during development and repair. We investigated the expression of Sprouty isoforms in hippocampal neurons as well as the regulation of Sprouty2 and -4 during development and their role in axon growth. Sprouty2 and -4 were located in the nucleus, the cytoplasm, in dendrites, and axons of hippocampal neurons concentrated in growth cones. During development in vivo and differentiation in vitro, expression of Sprouty2 and -4 was gradually downregulated in hippocampal neurons. Between 5 and 24 days in culture expression of both Sprouty isoforms was reduced by 70%. In vivo expression of Sprouty2 was reduced by 79% and of Sprouty4 by 93% on postnatal day 14 compared to embryonic day 16.5. Downregulation of Sprouty2 and -4 by shRNAs strongly promoted elongative axon growth by cultured hippocampal neurons, which was further increased by FGF-2 treatment. In addition, FGF-2 reduced expression of Sprouty2 by 33% and of Sprouty4 by 44%. Together, our results imply that Sprouty2 and -4 are downregulated in the hippocampus during postnatal brain development and that they can act as regulators of developmental axon growth.
芽蛋白作为成纤维细胞生长因子 (FGF) 信号的负反馈抑制剂。FGF 属于神经营养因子，参与发育和修复过程中的轴突生长。我们研究了 Sprouty 同工型在海马神经元中的表达，以及 Sprouty2 和 -4 在发育过程中的调节及其在轴突生长中的作用。Sprouty2 和 -4 位于海马神经元的细胞核、细胞质、树突和轴突中，集中在生长锥中。在体内发育和体外分化过程中，海马神经元中的 Sprouty2 和 -4 表达逐渐下调。在培养的第 5 天至第 24 天，两种 Sprouty 同工型的表达减少了 70%。与胚胎第 16.5 天相比，在体 Sprouty2 的表达在出生后第 14 天减少了 79%，Sprouty4 的表达减少了 93%。shRNA 下调 Sprouty2 和 -4 可强烈促进培养的海马神经元的伸长轴突生长，而 FGF-2 处理则进一步增加了这种作用。此外，FGF-2 将 Sprouty2 的表达降低了 33%，将 Sprouty4 的表达降低了 44%。总之，我们的研究结果表明，Sprouty2 和 -4 在出生后大脑发育过程中在海马体中下调，并且它们可以作为发育性轴突生长的调节剂。
