Affiliation:
1. Department of Anatomy and Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Abstract
Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: They become repelled by the repellent Slit and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. Here, we provide evidence that these two changes are causally linked: In the growth cones of embryonic
Xenopus
spinal axons, activation of the Slit receptor Roundabout (Robo) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation.
Publisher
American Association for the Advancement of Science (AAAS)
Reference39 articles.
1. The Molecular Biology of Axon Guidance
2. Slit Is the Midline Repellent for the Robo Receptor in Drosophila
3. Squeezing Axons Out of the Gray Matter
4. Change in Chemoattractant Responsiveness of Developing Axons at an Intermediate Target
5. In vitro Xenopus fertilization was performed as described [N. Tabti M.-M. Poo in Culturing Nerve Cells G. Banker K. Goslin Eds. (MIT Press Cambridge MA 1991)]. Messenger RNA was injected into the second blastomere of Xenopus embryos at the four-cell stage as described (7); mRNA encoding GFP was coinjected and GFP was used as an indicator for expression of the sample mRNA in a cell. Cultures of Xenopus spinal neurons were prepared from neural tube tissue of st. 22 embryos or from st. 28 where indicated as described [
Cited by
509 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献