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Published September 25, 2008 | Accepted Version + Supplemental Material + Published
Journal Article Open

A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection


In Drosophila embryos and larvae, a small number of identified motor neurons innervate body wall muscles in a highly stereotyped pattern. Although genetic screens have identified many proteins that are required for axon guidance and synaptogenesis in this system, little is known about the mechanisms by which muscle fibers are defined as targets for specific motor axons. To identify potential target labels, we screened 410 genes encoding cell-surface and secreted proteins, searching for those whose overexpression on all muscle fibers causes motor axons to make targeting errors. Thirty such genes were identified, and a number of these were members of a large gene family encoding proteins whose extracellular domains contain leucine-rich repeat (LRR) sequences, which are protein interaction modules. By manipulating gene expression in muscle 12, we showed that four LRR proteins participate in the selection of this muscle as the appropriate synaptic target for the RP5 motor neuron.

Additional Information

© 2008 Elsevier Inc. Accepted: July 29, 2008. Published: September 24, 2008. We thank members of the Zinn and Suzuki groups, Akinao Nose, and Liqun Luo for helpful discussions, Violana Nesterova for technical assistance, figure preparation, and the gene name, Susan Ou for antibody work, Liqun Luo for the LL01240 insertion mutant, Stephen Cohen for the trn caps double mutant, Akinao Nose for UAS-Caps and anti-Caps antibody, and Allen Laughon for anti-Trn antibody. We also thank FlyBase, the Bloomington, Szeged, Kyoto, and Harvard stock centers, GenExel, Inc., the VDRC, and the National Institute of Genetics for information and fly stocks. This work was supported by an NIH RO1 grant to K.Z., NS28182, by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Naito Foundation to M.K., and by a grant from the Mitsubishi Foundation to E.S. M.K. was supported as a postdoc at Caltech by a Postdoctoral Fellowship for Research Abroad of the Japan Society for the Promotion of Science for Young Scientists. Confocal analysis was performed at the Caltech Biological Imaging Facility. Mouse antisera were generated by the Caltech Monoclonal Antibody Facility. The Supplemental Data include eight figures, four tables, and Supplemental Text and can be found with this article online at http://www.neuron.org/cgi/content/full/59/6/972/DC1/.

Attached Files

Published - KURneu08_supp2.xls

Published - KURneu08_supp5.xls

Accepted Version - nihms71596.pdf

Supplemental Material - KURneu08_supp1.pdf

Supplemental Material - KURneu08_supp3.xls

Supplemental Material - KURneu08_supp4.xls


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