Anterograde jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila

Anterograde jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila
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DOI:
10.1016/j.cell.2007.02.024
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发表时间:
2007-03-09
期刊:
影响因子:
64.5
通讯作者:
Salecker, Iris
Salecker, Iris
中科院分区:
生物学1区
文献类型:
--
作者:
Bazigou, Eleni;Apitz, Holger;Salecker, Iris

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根据其在脊椎动物和无脊椎动物中的表达模式,间变性淋巴瘤激酶 (Alk) 被认为可以调节神经元发育;然而,其在体内的功能尚不清楚。我们证明 Alk 及其配体 Jelly belly (Jeb) 在果蝇视觉系统中作为顺行信号通路介导神经元回路组装发挥着核心作用。 Alk 在视叶的目标神经元中表达和需要,而 Jeb 主要由光感受器轴突产生,并在眼睛中发挥作用,控制椎板中 R1-R6 轴突和髓质中 R8 轴突的目标选择。 Jeb/Alk 功能受损会影响髓质中三种细胞粘附分子 Dumbfounded/Kirre、Roughest/IrreC 和 Flamingo 的层特异性表达。此外,目标神经元中火烈鸟的缺失会导致在 jeb 和 Alk 镶嵌动物中观察到的一些 R8 轴突靶向错误。总之,这些发现表明 Jeb/Alk 信号传导有助于 R 细胞轴突塑造目标识别环境。
Anaplastic lymphoma kinase (Alk) has been proposed to regulate neuronal development based on its expression pattern in vertebrates and invertebrates; however, its function in vivo is unknown. We demonstrate that Alk and its ligand Jelly belly (Jeb) play a central role as an anterograde, signaling pathway mediating neuronal circuit assembly in the Drosophila visual system. Alk is expressed and required in target neurons in the optic lobe, whereas Jeb is primarily generated by photoreceptor axons and functions in the eye to control target selection of R1-R6 axons in the lamina and R8 axons in the medulla. Impaired Jeb/Alk function affects layer-specific expression of three cell-adhesion molecules, Dumbfounded/Kirre, Roughest/IrreC, and Flamingo, in the medulla. Moreover, loss of flamingo in target neurons causes some R8-axon targeting errors observed in jeb and Alk mosaic animals. Together, these findings suggest that Jeb/Alk signaling helps R-cell axons to shape their environment for target recognition.