Callahan C A, Muralidhar M G, Lundgren S E, Scully A L, Thomas J B
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186, USA.
Nature. 1995 Jul 13;376(6536):171-4. doi: 10.1038/376171a0.
During development, neurons are capable of selecting specific pathways that lead them to their appropriate target areas. A variety of molecular mechanisms are thought to be involved in pathway recognition, including cell adhesion, repulsion and chemotropism. However, apart from a few genes whose involvement has been shown genetically, the mechanisms underlying neuronal pathway selection are largely unknown. Here we report the isolation of the Drosophila derailed (drl) gene, which encodes a novel member of the receptor protein-tyrosine kinase family. Using a newly developed axon-targeted reporter gene we find that drl is expressed by a small subset of embryonic interneurons whose growth cones choose common pathways during development. In drl mutant embryos these neurons fail to make the correct pathway choices. Our results provide evidence for receptor protein-tyrosine kinase involvement in key aspects of neuronal pathway recognition.
在发育过程中,神经元能够选择特定的路径,引导它们到达合适的目标区域。人们认为多种分子机制参与路径识别,包括细胞黏附、排斥和化学趋向性。然而,除了少数几个已通过遗传学方法证明其参与的基因外,神经元路径选择背后的机制在很大程度上尚不清楚。在此,我们报告了果蝇脱轨(drl)基因的分离,该基因编码受体蛋白酪氨酸激酶家族的一个新成员。使用新开发的轴突靶向报告基因,我们发现drl由一小部分胚胎中间神经元表达,这些神经元的生长锥在发育过程中选择共同的路径。在drl突变胚胎中,这些神经元无法做出正确的路径选择。我们的结果为受体蛋白酪氨酸激酶参与神经元路径识别的关键方面提供了证据。