The transcription factor Engrailed-2 guides retinal axons

Isabelle Brunet, Christine Weinl, Michael Piper, Alain Trembleau, Michel Volovitch, William Harris, Alain Prochiantz () and Christine Holt ()
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Isabelle Brunet: CNRS UMR 8542, Ecole Normale Supérieure
Christine Weinl: University of Cambridge
Michael Piper: University of Cambridge
Alain Trembleau: CNRS UMR 8542, Ecole Normale Supérieure
Michel Volovitch: CNRS UMR 8542, Ecole Normale Supérieure
William Harris: University of Cambridge
Alain Prochiantz: CNRS UMR 8542, Ecole Normale Supérieure
Christine Holt: University of Cambridge

Nature, 2005, vol. 438, issue 7064, 94-98

Abstract: Abstract Engrailed-2 (En-2), a homeodomain transcription factor, is expressed in a caudal-to-rostral gradient in the developing midbrain, where it has an instructive role in patterning the optic tectum—the target of topographic retinal input1,2. In addition to its well-known role in regulating gene expression through its DNA-binding domain, En-2 may also have a role in cell–cell communication, as suggested by the presence of other domains involved in nuclear export, secretion and internalization3. Consistent with this possibility, here we report that an external gradient of En-2 protein strongly repels growth cones of Xenopus axons originating from the temporal retina and, conversely, attracts nasal axons. Fluorescently tagged En-2 accumulates inside growth cones within minutes of exposure, and a mutant form of the protein that cannot enter cells fails to elicit axon turning. Once internalized, En-2 stimulates the rapid phosphorylation of proteins involved in translation initiation and triggers the local synthesis of new proteins. Furthermore, the turning responses of both nasal and temporal growth cones in the presence of En-2 are blocked by inhibitors of protein synthesis. The differential guidance of nasal and temporal axons reported here suggests that En-2 may participate directly in topographic map formation in the vertebrate visual system.

Date: 2005
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DOI: 10.1038/nature04110

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