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The Journal of Neuroscience, October 22, 2008, 28(43):10875-10884; doi:10.1523/JNEUROSCI.0164-08.2008

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Development/Plasticity/Repair
Presynaptic Local Signaling by a Canonical Wingless Pathway Regulates Development of the Drosophila Neuromuscular Junction

Claudia Miech,¹ Hans-Ulrich Pauer,² Xi He,¹ and Thomas L. Schwarz^1,3

¹F. M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachusetts 02115, ²Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, and ³Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to Thomas L. Schwarz, Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115. Email: thomas.schwarz{at}childrens.harvard.edu

Wnt/wingless signaling contributes to the development of neuronal synapses, including the Drosophila neuromuscular junction. Loss of wg (wingless) function alters the number and structure of boutons at this model synapse. Examining Wnt/wingless signaling mechanisms, we find that a distinct pathway operates presynaptically in the motoneuron and can account for many of the effects of wingless at this synapse. This pathway includes the canonical elements arrow/LRP (low-density lipoprotein receptor-related protein), dishevelled, and the glycogen synthase kinase shaggy (GSK3) and regulates the formation of microtubule loops within synaptic boutons as well as the number of synaptic boutons. This pathway, however, appears to be independent of β-catenin signaling and the transcriptional regulation that is most frequently downstream of these components. Instead, inhibition of shaggy is likely to act locally. This pathway thus provides a parallel mechanism to the postsynaptic activation of frizzled receptors and indicates that synaptic development results from the bidirectional influence of wingless on both presynaptic and postsynaptic structures via distinct intracellular pathways.

Key words: canonical wingless signaling; synaptic; shaggy; futsch; Drosophila;; neuromuscular junction

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Received Aug. 20, 2008; accepted Sept. 4, 2008.

Correspondence should be addressed to Thomas L. Schwarz, Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115. Email: thomas.schwarz{at}childrens.harvard.edu

This article has been cited by other articles:

				G. G. Farias, I. E. Alfaro, W. Cerpa, C. P. Grabowski, J. A. Godoy, C. Bonansco, and N. C. Inestrosa Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons J. Biol. Chem., June 5, 2009; 284(23): 15857 - 15866. [Abstract] [Full Text] [PDF]

				A. Chiang, R. Priya, M. Ramaswami, K. VijayRaghavan, and V. Rodrigues Neuronal activity and Wnt signaling act through Gsk3-{beta} to regulate axonal integrity in mature Drosophila olfactory sensory neurons Development, April 15, 2009; 136(8): 1273 - 1282. [Abstract] [Full Text] [PDF]

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