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First published online 28 February 2006
doi: 10.1242/jcs.02832


Journal of Cell Science 119, 1118-1129 (2006)
Published by The Company of Biologists 2006
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Research Article

Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis

Hiroshi Kimura1, Tadao Usui2, Asako Tsubouchi2,3 and Tadashi Uemura2,3,*

1 Department of Biophysics, Graduate School of Science, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8507, Japan
2 Graduate School of Biostudies, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8507, Japan
3 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan

* Author for correspondence (e-mail: tauemura{at}lif.kyoto-u.ac.jp)

Accepted 8 December 2005

Seven-pass transmembrane cadherins (7-TM cadherins) play pleiotropic roles in epithelial planar cell polarity, shaping dendritic arbors and in axonal outgrowth. In contrast to their role in planar polarity, how 7-TM cadherins control dendritic and axonal outgrowth at the molecular level is largely unknown. Therefore, we performed extensive structure-function analysis of the Drosophila 7-TM cadherin Flamingo (Fmi) and investigated the activities of individual mutant forms mostly in dendritogenesis of dendritic arborization (da) neurons. One of the fmi-mutant phenotypes was overgrowth of branches in the early stage of dendrite development. In da neurons but not in their adjacent non-neuronal cells, expression of a truncated form ({Delta}N) that lacks the entire cadherin repeat sequence, rescues flies - at least partially - from this phenotype. Another phenotype is observed at a later stage, when dendritic terminals outgrowing from the contralateral sides meet and then avoid each other. In the fmi mutant, by contrast, those branches overlapped. Overexpression of the {Delta}N form on the wild-type background phenocopied the overlap phenotype in the mutant, and analysis in heterologous systems supported the possibility that this effect might be because the Fmi-Fmi homophilic interaction is inhibited by {Delta}N. We propose that a dual molecular function of Fmi play pivotal roles in dendrite morphogenesis. In the initial growing phase, Fmi might function as a receptor for a sofar-unidentified ligand and this hypothetical heterophilic interaction would be responsible for limiting branch elongation. At a later stage, homophilic Fmi-binding at dendro-dendritic interfaces would elicit avoidance between dendritic terminals.

Key words: Cadherin superfamily, Flamingo, Dendrite, Drosophila


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