Dr. Bruno Marie
Adjunct Professor (Assistant Professor of Institute of Neurobiology) Institute of Neurobiology, Lab 314
Interests: My laboratory is using the powerful tools of Drosophila genetics to answer basic questions regarding synapse function and development.
1)The molecular control of Synaptic Growth The synapse of the neuromuscular junction (NMJ) is composed of a series of varicosities (the synaptic boutons) that contain the presynaptic machinery and oppose the muscle cell. My laboratory works on understanding the signaling mechanisms that generate presynaptic boutons and that control the growth of the synapse.
I previously characterized mutants of the synaptic multiâ€“adaptor protein Dap160, the ortholog of the mammalian Intersectin. I showed that this molecule scaffolds the endocytic machinery at the synapse and also regulates synaptic growth. The data I collected lead me to present a model in which the scaffolding protein Dap160 coordinates, within the periactive zone, synaptic signaling systems necessary for synaptic growth and is also responsible for efficient vesicle recycling at the NMJ (Marie et al, Neuron 2004). I have also carried out a genetic screen that links Dap160 to the regulation of cytoskeleton dynamics. My lab is now characterizing molecules regulating cytoskeleton dynamics at the synapse.
2)The molecular control of Synaptic Homeostasis
My laboratory is also exploring how homeostatic signaling can modulate synaptic release. Homeostasis is a form of feedback regulation that precisely maintains the function of a system at a set point level of activity. Within the nervous system, homeostatic signaling systems are thought to constrain plasticity to ensure neural activity will remain stable over time. As such, homeostatic mechanisms are thought to be the mechanisms that prevent the nervous system to fall into chaos and impairment of such mechanisms has been hypothesized to be responsible for epilepsy. However, the molecular mechanisms of homeostasis in the nervous system are virtually unknown. Homeostatic control of neuronal activity has been shown to occur in the CNS and PNS of both vertebrates and invertebrates following perturbation of neuron or muscle excitability. Homeostatic regulation of synaptic strength has been demonstrated at the Drosophila (NMJ). The Drosophila NMJ is a glutamatergic synapse. Manipulations that decrease the sensitivity of postsynaptic glutamate receptors (GluR), cause a compensatory, homeostatic increase in presynaptic neurotransmitter release (see diagram). This increase in presynaptic neurotransmitter release precisely counteracts the decrease in postsynaptic receptor sensitivity allowing normal muscle contraction. In collaboration with the lab of Graeme Davis (UCSF), my laboratory has carried out a screen allowing the identification of molecules involved in homeostatic compensation. These molecules, ranging from transcription factor to ion channel are now under study.
Marie B, Pym E, Bergquist S, Davis GW. (2010) Synaptic homeostasis is consolidated by the cell fate gene gooseberry, a Drosophila pax3/7 homolog. J Neurosci 30(24):8071-8082.
- Booth D, Marie B, Domenici P, Blagburn JM, Bacon JP. (2009) Transcriptional control of behavior: engrailed knock-out changes cockroach escape trajectories. J Neurosci. Jun 3;29(22):7181-90.
- Marie B, Sweeney ST, Poskanzer KE, Roos J, Kelly RB, Davis GW (2004)Dapl60/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth. Neuron. 43: 207-219.
- Marie B, Blagburn JM (2003). Differential roles of Engrailed paralogs in determining sensory axon guidance and synaptic target recognition. Journal of Neuroscience 23: 7854-7862.
- Soto I, Marie B, Baro DJ, Blanco RE (2003). FGF-2 modulates the expression and distribution of GAP-43 in frog retinal ganglion cells after optic nerve injury. Journal of Neuroscience Research 73: 507-517.
- Marie B, Cruz-Orengo L and Blagburn JM (2002). Persistent Engrailed expression is required to determine sensory axon trajectory, branching, and target choice. Journal of Neuroscience 22: 832-841.
- Marie B, Bacon JP and Blagburn JM. (2000). Double-stranded RNA interference shows that Engrailed controls the synaptic specificity of identified sensory neurons. Current Biology 10: 289-292.
Marie B, Bacon JP (2000). Two engrailed-related genes in the cockroach: cloning, phylogenetic analysis, expression and isolation of spliced variants. Development, Genes and Evolution 210: 436-448.
Marie B, Pym E, Pielage J, Eaton, BJ, Davis GW. (2008) Gooseberry, the Drosophila Pax3/Pax7 homolog, is necessary in postembryonic neurons for synaptic homeostasis. Society for Neuroscience Annual Meeting. Washington DC, 635.10/F1.
Marie B, Pym E, Pielage J, Davis GW. (2008) Gooseberry, the Drosophila Pax3/Pax7 homolog, is necessary in post mitotic neurons for synaptic homeostasis. FENS 2008 â€“ Geneva, Switzerland.