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Published August 10, 2004 | Supplemental Material
Journal Article Open

Roundabout 2 Regulates Migration of Sensory Neurons by Signaling In trans


Background: Roundabout (Robo) receptors and their ligand Slit are important regulators of axon guidance and cell migration. The development of Drosophila embryonic sense organs provides a neuronal migration paradigm where the in vivo roles of Slit and Robo can be assayed using genetics. Results: Here we show that Slit-Robo signaling controls migration of Drosophila larval sensory neurons that are part of the Chordotonal (Cho) stretch receptor organs. We used live imaging to show that abdominal Cho organs normally migrate ventrally during development, whereas thoracic Cho organs do not. Robo2 overexpression in cis (in the sensory neurons) or in trans (on neighboring visceral mesoderm) transforms abdominal organs to a thoracic morphology and position by blocking migration, while loss of Slit-Robo signaling produces a reverse transformation in which thoracic organs migrate ectopically. Rescue and tissue-specific knockout experiments indicate that trans signaling by Robo2 contributes to the normal positioning of the thoracic Cho organs. The differential positioning of Cho organs between the thorax and abdomen is known to be regulated by Hox genes, and we show that the essential Hox cofactor Homothorax, represses Robo2 expression in the abdominal visceral mesoderm. Conclusions: Our results suggest that segment-specific neuronal migration patterns are directed through a novel signaling complex (the "Slit sandwich") in which Robo2 on the thoracic visceral mesoderm binds to Slit and presents it to Robo receptors on Cho neurons. The differential positioning of Cho organs between thorax and abdomen may be determined by Hox gene-mediated repression of robo2.

Additional Information

© 2004 Elsevier Ltd. Received 16 October 2003, Revised 8 June 2004, Accepted 21 June 2004, Available online 5 August 2004. Published: August 10, 2004. We are very grateful to Aloisia Schmid for doing the DiI injections in Figure 3. We thank the members of the Zinn group, Peter Kolodziej, Richard Mann, Julie Simpson, and Greg Bashaw for helpful discussions; Julie Simpson, Greg Bashaw, Richard Mann, Bassem Hassan, Hugo Bellen, and Marc Halfon for constructs and fly stocks; Srikanth Rajagopalan, Sunita Kramer, and Dan Tracey for antibodies; and Cyrus Papan and Dan Darcy for their expert help with imaging. Imaging work was performed at the Caltech Biological Imaging Facility. This work was supported by an NIH RO1 grant, NS28182, to K.Z. R.K. was supported by an NIH postdoctoral fellowship.

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