UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation
UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation
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DOI：
10.1038/nn1666
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发表时间：
2006-04-01
影响因子：
25
通讯作者：
Bargmann, CI
中科院分区：
文献类型：
--
作者：
Adler, CE;Fetter, RD;Bargmann, CI
UNC-6/Netrin及其受体UNC-40/DCC是生长锥调节的保守调节因子。通过在体内直接观察发育中的神经元，我们发现UNC-6和UNC-40在轴突形成过程中也起着启动、维持和定向不对称神经元生长的作用。秀丽线虫未成熟的HSN神经元打破了球对称，向腹侧UNC-6延伸前沿。在UNC-6和UNC-40突变体中，前沿形成失败，细胞直到发育后期都保持对称，最终形成的轴突被误导。因此，netrin有两种活动：一种是破坏神经元的对称性，另一种是引导未来的轴突。随着轴突的形成，UNC-6、UNC-40以及脂质调节剂AGE-1/PI3K和DAF-18/PTEN驱动HSN中肌动蛋白调节的Pleckstrin同源(PH)结构域蛋白MIG-10/lamellipodin腹向促进不对称生长。定向netrin信号通过PI3K信号耦合到持续的不对称生长，这让人想起趋化细胞的极化。
UNC-6/Netrin and its receptor UNC-40/DCC are conserved regulators of growth cone guidance. By directly observing developing neurons in vivo, we show that UNC-6 and UNC-40 also function during axon formation to initiate, maintain and orient asymmetric neuronal growth. The immature HSN neuron of Caenorhabditis elegans breaks spherical symmetry to extend a leading edge toward ventral UNC-6. In unc-6 and unc-40 mutants, leading edge formation fails, the cell remains symmetrical until late in development and the axon that eventually forms is misguided. Thus netrin has two activities: one that breaks neuronal symmetry and one that guides the future axon. As the axon forms, UNC-6, UNC-40 and the lipid modulators AGE-1/phosphoinositide 3-kinase (PI3K) and DAF-18/PTEN drive the actin-regulatory pleckstrin homology (PH) domain protein MIG-10/lamellipodin ventrally in HSN to promote asymmetric growth. The coupling of a directional netrin cue to sustained asymmetric growth via PI3K signaling is reminiscent of polarization in chemotaxing cells.