Axon Guidance

Comm Keeps Robo Down

Science's STKE  27 Aug 2002:
Vol. 2002, Issue 147, pp. tw312-TW312
DOI: 10.1126/stke.2002.147.tw312

Some axons will cross the midline to innervate the contralateral side of the animal. The developing Drosophila nervous system has provided a model system for studying the molecular mechanisms underlying the movement of axons at the midline. Neurons that express the Robo receptor are repelled from crossing the midline by the Slit ligand produced by the midline cells; whereas neurons migrate across the midline in response to the chemoattractant Netrins, which interact with the Frazzled receptor. To prevent recrossing of the midline, Robo is up-regulated once the neurons reach the contralateral side. Kelemann et al. provide evidence that the regulation of Robo occurs through the actions of the commissureless (comm) gene product and involves the regulation of the intracellular trafficking of Robo by Comm. Using cell transplantation studies, the authors determined that Comm function was important in the neuron and not the midline glia for allowing midline crossing. Neurons that crossed the midline displayed high levels of comm expression at the time the axons were crossing the midline, and expression was much lower before and after midline crossing. Neurons that did not cross the midline did not express comm. When expressed in cultured COS cells, Robo was detected at the cell surface, but when coexpressed with Comm, Robo was detected in late endosomes and lysosomes along with Comm. Comm and Comm-deletion constructs that were competent to sort Robo in transfected cultured cells into the endosomal-lysosomal compartment also produced robo-like phenotypes in Drosophila. Thus, Comm appears to control Robo function by preventing cell-surface expression of Robo during the period of midline crossing.

K. Keleman, S. Rajagopalan, D. Cleppien, D. Teis, K. Paiha, L. A. Huber, G. M. Tachnau, B. J. Dickson, Comm sorts Robo to control axon guidance at the Drosophila midline. Cell 110, 415-427 (2002). [Online Journal]