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Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc)
Sylvie Le Guyader1,
Klaus Scholich3, and
1 Developmental Neurobiology Group, Temasek Life Sciences Laboratory, 1 Research
Link, Singapore 117604, Rep. of Singapore 2 Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076
Tübingen, Germany 3 Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität
Frankfurt, 60590 Frankfurt, Germany
Author for correspondence (e-mail:
Accepted for publication 29 October 2004.
Visual system development is dependent on correct interpretationof cues
that direct growth cone migration and axon branching.Mutations in the
zebrafish esrom gene disrupt bundling and targetingof retinal axons,
and also cause ectopic arborization. By positionalcloning, we establish that
esrom encodes a very large proteinorthologous to PAM (protein
associated with Myc)/Highwire/RPM-1.Unlike motoneurons in Drosophila
highwire mutants, retinal axonsin esrom mutants do not arborize
excessively, indicating thatEsrom has different functions in the vertebrate
visual system.We show here that Esrom has E3 ligase activity and modulates
theamount of phosphorylated Tuberin, a tumor suppressor, in growthcones.
These data identify a mediator of signal transductionin retinal growth cones,
which is required for topographic mapformation.