Neuron
Volume 64, Issue 3, 12 November 2009, Pages 355-366
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Article
Extracellular Engrailed Participates in the Topographic Guidance of Retinal Axons In Vivo

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Summary

Engrailed transcription factors regulate the expression of guidance cues that pattern retinal axon terminals in the dorsal midbrain. They also act directly to guide axon growth in vitro. We show here that an extracellular En gradient exists in the tectum along the anterior-posterior axis. Neutralizing extracellular Engrailed in vivo with antibodies expressed in the tectum causes temporal axons to map aberrantly to the posterior tectum in chick and Xenopus. Furthermore, posterior membranes from wild-type tecta incubated with anti-Engrailed antibodies or posterior membranes from Engrailed-1 knockout mice exhibit diminished repulsive activity for temporal axons. Since EphrinAs play a major role in anterior-posterior mapping, we tested whether Engrailed cooperates with EphrinA5 in vitro. We find that Engrailed restores full repulsion to axons given subthreshold doses of EphrinA5. Collectively, our results indicate that extracellular Engrailed contributes to retinotectal mapping in vivo by modulating the sensitivity of growth cones to EphrinA.

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7

These authors contributed equally to this work

8

Present address: Institute for Cell Biology, Department of Molecular Biology, University of Tuebingen, Auf der Morgenstelle 15, D-72076 Tuebingen, Germany

9

Present address: Institut of Anatomy, Department of Experimental Embryology, University of Tuebingen, Oesterbergstrasse 3, D-72074 Tuebingen, Germany

10

Present address: College de France, Inserm U833, 11 Place Marcelin Berthelot, F-75005 Paris, France

11

Present address: University of California, Davis Medical Center, Department of Pathology, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817, USA