Getting Frazzled in Axon Guidance

Science's STKE  29 Aug 2000:
Vol. 2000, Issue 47, pp. tw1
DOI: 10.1126/stke.2000.47.tw1

In Drosophila, Netrins and their receptors DCC and Unc-5 are known to be important for proper axon guidance. However, Hiramoto et al. demonstrate that photoreceptors adopt a different mechanism of target guidance involving Netrin and Frazzled, a protein orthologous to DCC. Netrin transcripts and Netrin protein do not colocalize; Netrin protein localizes to the dorsolateral region, highly overlapping with the distribution of Frazzled. The specific localization of Frazzled depends on its cytoplasmic domain. The Drosophila pioneer neuron dMP2 requires proper localization of Netrin and Frazzled for its migration; however, the authors demonstrated that Frazzled does not act in a cell-autonomous manner (where Frazzled would act as a sensor for Netrin), but in fact, Frazzled acts as an attractant (with Netrin) to guide migrating neurons. Because the dMP2 neuron does not express Frazzled protein, this implies that another, uncharacterized receptor is expressed by dMP2 to bind Frazzled-captured Netrin and to send signals inside the migrating dMP2 neuron.

Hiramoto, M., Hiromi, Y., Giniger, E., and Hotta, Y. (2000) The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution. Nature 406: 886-889. [Online Journal]