Axon Guidance

Combinatorial Receptors

Science's STKE  05 Nov 2002:
Vol. 2002, Issue 157, pp. tw408-TW408
DOI: 10.1126/stke.2002.157.tw408

Yu et al. used the model organism Caenorhabditis elegans to investigate mechanisms underlying axon guidance for various neurons by analyzing axon migration patterns in worms with combinations of mutations in various genes. They determined that the phenotypes for unc-34 (encoding the Enabled protein) and sax-3 (encoding the Slit receptor Robo) were in many cases similar and that epistasis analysis suggested that these two genes function in the same pathway to control axon repulsion. More interesting was the interaction they detected between unc-34, sax-3, and unc-40 (encoding the receptor DCC for Netrin). Netrin and Slit often produce opposing guidance cues. However, the interaction between unc-34, sax-3, and unc-40 suggested that the role for DCC in mediating axon repulsion was independent of its role as a Netrin receptor. In vitro biochemical interactions were detected between Enabled and Robo, between DCC and Robo, and for Robo with itself. The authors suggest that recruitment of different receptors with different cytoplasmic domains may allow local integration of guidance cues, which allows different responses in different parts of the moving growth cone.

T. W. Yu, J. C. Hao, W. Lim, M. Tessier-Lavigne, C. I. Bargmann, Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nature Neurosci. 5, 1147-1154 (2002). [Online Journal]