Nature Neuroscience 9, 58 - 66 (2005)
Published online: 11 December 2005; | doi:10.1038/nn1612
ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized NetrinMasaki Hiramoto1, 2, 3
& Yasushi Hiromi1, 4, 51
Department of Developmental Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. 2
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012 Japan. 3
Japan Society for the Promotion of Science, SOKENDAI, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. 4
Department of Genetics, SOKENDAI, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. 5
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Correspondence should be addressed to Masaki Hiramoto hiramoto@pb3.so-net.ne.jp or Yasushi Hiromi yhiromi@lab.nig.ac.jp Networks in the CNS consist of neural modules that are connected in a repetitive array. Whereas individual modules contain guidance information along which axons track within the unit, these guidance cues hinder axon extension across module boundaries. We investigated how axons solve this 'boundary problem' by analyzing the longitudinal connections of neuromeres in Drosophila melanogaster. The initial trajectory of the longitudinal axons is guided by Netrin, which is localized on commissural axons by its receptor, Frazzled. The Netrin cue on the commissure of the next segment can act as a barrier to longitudinal axons, inhibiting their extension and misguiding them contralaterally along the commissure. We show that, before reaching the segmental boundary, the longitudinal axons' responsiveness to Netrin presented on the commissure is suppressed by Roundabout (ROBO), through counteracting Gq signaling. The absence of suppression causes the robo phenotype: longitudinal axons project toward the midline, as if running around a roundabout (rotary).
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