The transcription factor Engrailed-2 guides retinal axons.
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 input. 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 internalization. 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.
Brunet
Isabelle
I
CNRS UMR 8542, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
Weinl
Christine
C
Piper
Michael
M
Trembleau
Alain
A
Volovitch
Michel
M
Harris
William
W
Prochiantz
Alain
A
Holt
Christine
C
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D020439:Growth Cones / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D009666:Nose / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology; D014981:Xenopus / Q000196:embryology; D000099266:Engrailed 2 Protein
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000099266:Engrailed 2 Protein