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Extracellular engrailed participates in the topographic guidance of retinal axons in vivo.
Neuron 64, 355-366 (2009)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
ganglion-cell axons; visual-system; optic tectum; growth cone; ephrin-as; nasotemporal polarity; transcription factor; tyrosine kinases; map development; messenger-RNA
ISSN (print) / ISBN
0896-6273
e-ISSN
1097-4199
Zeitschrift
Neuron
Quellenangaben
Band: 64,
Heft: 3,
Seiten: 355-366
Verlag
Elsevier
Verlagsort
Cambridge, Mass.
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Developmental Genetics (IDG)