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Published June 15, 2012 | Accepted Version
Journal Article Open

Developmental changes in expression, subcellular distribution, and function of Drosophila N-cadherin, guided by a cell-intrinsic program during neuronal differentiation


Cell adhesion molecules (CAMs) perform numerous functions during neural development. An individual CAM can play different roles during each stage of neuronal differentiation; however, little is known about how such functional switching is accomplished. Here we show that Drosophila N-cadherin (CadN) is required at multiple developmental stages within the same neuronal population and that its sub-cellular expression pattern changes between the different stages. During development of mushroom body neurons and motoneurons, CadN is expressed at high levels on growing axons, whereas expression becomes downregulated and restricted to synaptic sites in mature neurons. Phenotypic analysis of CadN mutants reveals that developing axons require CadN for axon guidance and fasciculation, whereas mature neurons for terminal growth and receptor clustering. Furthermore, we demonstrate that CadN downregulation can be achieved in cultured neurons without synaptic contact with other cells. Neuronal silencing experiments using Kir_2.1 indicate that neuronal excitability is also dispensable for CadN downregulation in vivo. Interestingly, downregulation of CadN can be prematurely induced by ectopic expression of a nonselective cation channel, dTRPA1, in developing neurons. Together, we suggest that switching of CadN expression during neuronal differentiation involves regulated cation influx within neurons.

Additional Information

© 2012 Elsevier Inc. Received 14 December 2011. Revised 2 April 2012. Accepted 3 April 2012. Available online 18 April 2012. We thank Drs. S. L. Zipursky, T. R. Clandinin, L. Luo, R. Okada, and T. Uemura as well as the Bloomington Stock Center and Developmental Studies Hybridoma Bank for generously providing the fly stocks, antibodies, and staining protocol. We also thank members of the Suzuki and Zinn groups for helpful discussions, A. Oishi and M. Taniguchi for technical assistance, and Y. Hiromi for the use of his laboratory to perform cell culture experiments. This work was supported by Grants-in-Aid for Scientific Research from MEXT Japan, Naito Foundation, and The Nakajima Foundation to M. K., and by NIH Grant RO1 NS062821 to K.Z.

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