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Development 132 (2): 247-256

Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc)

Jasmine D'Souza1, Michael Hendricks1, Sylvie Le Guyader1, Sivan Subburaju1, Barbara Grunewald2, Klaus Scholich3, and Suresh Jesuthasan1,*

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: suresh{at}

Accepted for publication 29 October 2004.

Abstract: Visual system development is dependent on correct interpretation of cues that direct growth cone migration and axon branching. Mutations in the zebrafish esrom gene disrupt bundling and targeting of retinal axons, and also cause ectopic arborization. By positional cloning, we establish that esrom encodes a very large protein orthologous to PAM (protein associated with Myc)/Highwire/RPM-1. Unlike motoneurons in Drosophila highwire mutants, retinal axons in esrom mutants do not arborize excessively, indicating that Esrom has different functions in the vertebrate visual system. We show here that Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. These data identify a mediator of signal transduction in retinal growth cones, which is required for topographic map formation.

Key Words: Retinotectal projection • Topographic mapping • Fasciculation • Axon branching • Visual system • Zebrafish

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