Compartmentalized Calcium Transients Trigger Dendrite Pruning in Drosophila Sensory Neurons

Dendritic Pruning During metamorphosis, Drosophila sensory neurons eliminate their dendritic trees, but axons and soma remain intact. Kanamori et al. (p. 1475, published online 30 May) demonstrate that compartmentalized calcium transients in dendrites function as the spatiotemporal cue for pruning of unwanted branches. Such a localized calcium signal, induced by a local elevation of branch excitability, activates calcium-dependent proteinases and eventually causes branch death. During fruit fly metamorphosis, dendritic calcium signaling defines the branches to be eliminated in sensory neurons. Dendrite pruning is critical for sculpting the final connectivity of neural circuits as it removes inappropriate projections, yet how neurons can selectively eliminate unnecessary dendritic branches remains elusive. Here, we show that calcium transients that are compartmentalized in specific dendritic branches act as temporal and spatial cues to trigger pruning in Drosophila sensory neurons. Calcium transients occurred in local dendrites at ~3 hours before branch elimination. In dendritic branches, intrinsic excitability increased locally to activate calcium influx via the voltage-gated calcium channels (VGCCs), and blockade of the VGCC activities impaired pruning. Further genetic analyses suggest that the calcium-activated protease calpain functions downstream of the calcium transients. Our findings reveal the importance of the compartmentalized subdendritic calcium signaling in spatiotemporally selective elimination of dendritic branches.

[1]  Y. Jan,et al.  Identification of E2/E3 Ubiquitinating Enzymes and Caspase Activity Regulating Drosophila Sensory Neuron Dendrite Pruning , 2006, Neuron.

[2]  C. Zuker,et al.  The Drosophila Light-Activated Conductance Is Composed of the Two Channels TRP and TRPL , 1996, Cell.

[3]  Y. Jan,et al.  Dendrite-specific remodeling of Drosophila sensory neurons requires matrix metalloproteases, ubiquitin-proteasome, and ecdysone signaling. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[4]  T. Gudermann,et al.  Drosophila TRPM Channel Is Essential for the Control of Extracellular Magnesium Levels , 2010, PloS one.

[5]  R. Wong,et al.  Activity-dependent regulation of dendritic growth and patterning , 2002, Nature Reviews Neuroscience.

[6]  P. O’Farrell,et al.  Nitric oxide synthase is not essential for Drosophila development , 2010, Current Biology.

[7]  Gilles Laurent,et al.  painless, a Drosophila Gene Essential for Nociception , 2003, Cell.

[8]  K. Emoto.  Signaling mechanisms that coordinate the development and maintenance of dendritic fields , 2012, Current Opinion in Neurobiology.

[9]  Y. Jan,et al.  Dendrites of Distinct Classes of Drosophila Sensory Neurons Show Different Capacities for Homotypic Repulsion , 2003, Current Biology.

[10]  D. Lynch,et al.  Calpain and synaptic function , 2006, Molecular Neurobiology.

[11]  K. Broadie,et al.  Motor Deficit in a Drosophila Model of Mucolipidosis Type IV due to Defective Clearance of Apoptotic Cells , 2008, Cell.

[12]  C. Montell,et al.  Control of thermotactic behavior via coupling of a TRP channel to a phospholipase C signaling cascade , 2008, Nature Neuroscience.

[13]  Sreekanth H. Chalasani,et al.  Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators , 2009, Nature Methods.

[14]  D. Van Vactor,et al.  Genetic and developmental characterization of Dmca1D, a calcium channel alpha1 subunit gene in Drosophila melanogaster. , 1998, Genetics.

[15]  Darren W. Williams,et al.  Local caspase activity directs engulfment of dendrites during pruning , 2006, Nature Neuroscience.

[16]  C. Zuker,et al.  Calmodulin Regulation of Drosophila Light-Activated Channels and Receptor Function Mediates Termination of the Light Response In Vivo , 1997, Cell.

[17]  William A Catterall,et al.  Voltage-Gated Calcium Channels , 2011 .

[18]  P. Detwiler,et al.  Directionally selective calcium signals in dendrites of starburst amacrine cells , 2002, Nature.

[19]  Darren W. Williams,et al.  Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons , 2005, Development.

[20]  T. Matsuo,et al.  Calcineurin and Its Regulator Sra/DSCR1 Are Essential for Sleep in Drosophila , 2011, The Journal of Neuroscience.

[21]  Liqun Luo,et al.  Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis , 1999, Neuron.

[22]  Judit K. Makara,et al.  Compartmentalized dendritic plasticity and input feature storage in neurons , 2008, Nature.

[23]  Feng Zhang,et al.  Channelrhodopsin-2 and optical control of excitable cells , 2006, Nature Methods.

[24]  D. Yamamoto,et al.  The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. , 1997, Development.

[25]  R. Srinivas,et al.  Genetic Dissection of itpr Gene Function Reveals a Vital Requirement in Aminergic Cells of Drosophila Larvae , 2004, Genetics.

[26]  D. Curtis,et al.  Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome , 2004, Nature Genetics.

[27]  J. C. Hall,et al.  Behavioral and cytogenetic analysis of the cacophony courtship song mutant and interacting genetic variants in Drosophila melanogaster. , 1987, Genetics.

[28]  M. Berridge,et al.  Calcium: Calcium signalling: dynamics, homeostasis and remodelling , 2003, Nature Reviews Molecular Cell Biology.

[29]  L. Luo,et al.  Axon retraction and degeneration in development and disease. , 2005, Annual review of neuroscience.

[30]  Y. Zhong,et al.  Altered synaptic plasticity in Drosophila memory mutants with a defective cyclic AMP cascade. , 1991, Science.

[31]  Michael Bate,et al.  Altered Electrical Properties in DrosophilaNeurons Developing without Synaptic Transmission , 2001, The Journal of Neuroscience.

[32]  T. Tully,et al.  Essential function of nitric oxide synthase in Drosophila , 2004, Current Biology.

[33]  G. Rubin,et al.  Refinement of Tools for Targeted Gene Expression in Drosophila , 2010, Genetics.

[34]  Zhefeng Gong,et al.  Two Interdependent TRPV Channel Subunits, Inactive and Nanchung, Mediate Hearing in Drosophila , 2004, The Journal of Neuroscience.

[35]  L. Levin,et al.  A calcium-inhibited Drosophila adenylyl cyclase. , 2000, Biochimica et biophysica acta.

[36]  Maurice J. Kernan,et al.  A TRPV family ion channel required for hearing in Drosophila , 2003, Nature.

[37]  B. Minke,et al.  TRP, a protein essential for inositide-mediated Ca2+ influx is localized adjacent to the calcium stores in Drosophila photoreceptors , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  Yongxin Zhao,et al.  An Expanded Palette of Genetically Encoded Ca2+ Indicators , 2011, Science.