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PMID:16267555

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Citation

Brunet, I, Weinl, C, Piper, M, Trembleau, A, Volovitch, M, Harris, W, Prochiantz, A and Holt, C (2005) The transcription factor Engrailed-2 guides retinal axons. Nature 438:94-8

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 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.

Links

PubMed Online version:10.1038/nature04110

Keywords

Animals; Axons/drug effects; Axons/metabolism; Endocytosis; Female; Growth Cones/drug effects; Homeodomain Proteins/metabolism; Homeodomain Proteins/pharmacology; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/pharmacology; Nose/cytology; Nose/drug effects; Nose/innervation; Phosphorylation/drug effects; Protein Biosynthesis/drug effects; Protein Transport; Retina/cytology; Retina/drug effects; Retina/embryology; Retina/metabolism; Retinal Ganglion Cells/cytology; Retinal Ganglion Cells/drug effects; Retinal Ganglion Cells/metabolism; Transcription Factors/metabolism; Transcription Factors/pharmacology; Vision, Ocular/drug effects; Vision, Ocular/physiology; Xenopus/embryology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:OTX2

located_in

GO:0030426: growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:OTX2

involved_in

GO:0007411: axon guidance

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:HME2

located_in

GO:0030426: growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

located_in

GO:0030175: filopodium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

located_in

GO:0043005: neuron projection

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

located_in

GO:0030027: lamellipodium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

involved_in

GO:0007411: axon guidance

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:HME2

part_of

GO:0030027: lamellipodium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

part_of

GO:0030175: filopodium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

part_of

GO:0030426: growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

involved_in

GO:0042327: positive regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:HME2

part_of

GO:0043005: neuron projection

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:HME2

involved_in

GO:0045727: positive regulation of translation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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