Ectopic Expression in the Giant Fiber System ofDrosophila Reveals Distinct Roles for Roundabout (Robo), Robo2, and Robo3 in Dendritic Guidance and Synaptic Connectivity

The Roundabout (Robo) receptors have been intensively studied for their role in regulating axon guidance in the embryonic nervous system, whereas a role in dendritic guidance has not been explored. In the adult giant fiber system of Drosophila, we have revealed that ectopic Robo expression can regulate the growth and guidance of specific motor neuron dendrites, whereas Robo2 and Robo3 have no effect. We also show that the effect of Robo on dendritic guidance can be suppressed by Commissureless coexpression. Although we confirmed a role for all three Robo receptors in giant fiber axon guidance, the strong axon guidance alterations caused by overexpression of Robo2 or Robo3 have no effect on synaptic connectivity. In contrast, Robo overexpression in the giant fiber seems to directly interfere with synaptic function. We conclude that axon guidance, dendritic guidance, and synaptogenesis are separable processes and that the different Robo family members affect them distinctly.

[1]  B. Dickson,et al.  Selecting a Longitudinal Pathway Robo Receptors Specify the Lateral Position of Axons in the Drosophila CNS , 2000, Cell.

[2]  J. Bacon,et al.  Synaptogenesis in the giant-fibre system of Drosophila: interaction of the giant fibre and its major motorneuronal target. , 2000, Development.

[3]  Julie H. Simpson,et al.  Short-Range and Long-Range Guidance by Slit and Its Robo Receptors Robo and Robo2 Play Distinct Roles in Midline Guidance , 2000, Neuron.

[4]  R. Murphey,et al.  A Role for Drosophila Drac1 in Neurite Outgrowth and Synaptogenesis in the Giant Fiber System , 2000, Molecular and Cellular Neuroscience.

[5]  B. Dickson,et al.  Crossing the Midline Roles and Regulation of Robo Receptors , 2000, Neuron.

[6]  Julie H. Simpson,et al.  Short-Range and Long-Range Guidance by Slit and Its Robo Receptors A Combinatorial Code of Robo Receptors Controls Lateral Position , 2000, Cell.

[7]  C. Goodman,et al.  Repulsive Axon Guidance Abelson and Enabled Play Opposing Roles Downstream of the Roundabout Receptor , 2000, Cell.

[8]  A. Chiba,et al.  Axon pathfinding proceeds normally despite disrupted growth cone decisions at CNS midline. , 2000, Development.

[9]  Stephan J. Froggett,et al.  Targeted Expression of Truncated Glued Disrupts Giant Fiber Synapse Formation in Drosophila , 1999, The Journal of Neuroscience.

[10]  C. Goodman,et al.  Chimeric Axon Guidance Receptors The Cytoplasmic Domains of Slit and Netrin Receptors Specify Attraction versus Repulsion , 1999, Cell.

[11]  C. Goodman,et al.  Slit Is the Midline Repellent for the Robo Receptor in Drosophila , 1999, Cell.

[12]  J. Bacon,et al.  Null mutation in shaking‐B eliminates electrical, but not chemical, synapses in the Drosophila giant fiber system: A structural study , 1999, The Journal of comparative neurology.

[13]  M. Seeger,et al.  Commissureless endocytosis is correlated with initiation of neuromuscular synaptogenesis. , 1998, Development.

[14]  K. Moffat,et al.  Development of the giant fiber neuron of Drosophila melanogaster , 1998, The Journal of comparative neurology.

[15]  Marc Tessier-Lavigne,et al.  Roundabout Controls Axon Crossing of the CNS Midline and Defines a Novel Subfamily of Evolutionarily Conserved Guidance Receptors , 1998, Cell.

[16]  K. Inokuchi,et al.  vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long‐term potentiation and synaptogenesis 1 , 1997, FEBS letters.

[17]  M. Nieto Molecular Biology of Axon Guidance , 1996, Neuron.

[18]  C. Goodman,et al.  commissureless Controls Growth Cone Guidance across the CNS Midline in Drosophila and Encodes a Novel Membrane Protein , 1996, Neuron.

[19]  J. Bacon,et al.  Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  S. Benzer,et al.  bendless, a Drosophila gene affecting neuronal connectivity, encodes a ubiquitin-conjugating enzyme homolog , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  John B. Thomas,et al.  The Drosophila bendless gene encodes a neural protein related to ubiquitin-conjugating enzymes , 1993, Neuron.

[22]  C. Goodman,et al.  Mutations affecting growth cone guidance in drosophila: Genes necessary for guidance toward or away from the midline , 1993, Neuron.

[23]  J. Rothberg,et al.  slit: An EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system , 1988, Cell.

[24]  J. C. Hall,et al.  Identification of a cholinergic synapse in the giant fiber pathway of Drosophila using conditional mutations of acetylcholine synthesis. , 1984, Journal of neurogenetics.

[25]  R. Wyman,et al.  Mutations altering synaptic connectivity between identified neurons in Drosophila , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  R. Wyman,et al.  Motor outputs of giant nerve fiber in Drosophila. , 1980, Journal of neurophysiology.

[27]  R. Murphey,et al.  Controlling the motor neuron. , 1999, International review of neurobiology.

[28]  Claire Russell,et al.  Dosage-Sensitive and Complementary Functions of Roundabout and Commissureless Control Axon Crossing of the CNS Midline , 1998, Neuron.