Kate O'Connor-Giles

Molecular regulation of synaptic growth

Research Strengths: Development, Plasticity and Repair

Proper regulation of synaptic development and plasticity are fundamental to the function of neural circuits. Defects in synaptic growth are associated with a broad range of neurological disorders including developmental disorders; motor, cognitive and psychological impairments; and neurodegeneration. However, the molecular mechanisms regulating these processes are not well understood. Our research employs the Drosophila neuromuscular junction (NMJ) as a model system for dissecting the intrinsic and trans-synaptic mechanisms through which neurons and their targets coordinate the growth of synapses.

We are currently investigating the role of Nervous wreck in the negative regulation of synaptic growth. Nervous wreck is a member of a conserved family of proteins implicated in severe cognitive and motor deficits. This work has revealed a novel presynaptic endocytic mechanism for regulating neuronal responsiveness to postsynaptically derived growth signals during NMJ development. To identify additional regulators of synaptic growth, we have conducted genetic screens that have uncovered a number of novel molecules with previously unknown roles in synaptogenesis. They encode a diverse set of proteins that likely function in multiple aspects of synaptic development and represent a rich resource for uncovering the molecular mechanisms that govern synaptic growth.

Selected Publications:

Babaoglan, A.B., K.M. O’Connor-Giles, H. Mistry, A. Schickedanz, B.A. Wilson, and J.B. Skeath. Sanpodo: a context-dependent activator and inhibitor of Notch signaling during asymmetric divisions. Submitted.
O’Connor-Giles, K.M. and B. Ganetzky. 2008. Satellite Signaling at Synapses. Fly 2:259-61.
O’Connor-Giles, K.M., L.L. Ho, and B. Ganetzky. 2008. Nervous wreck interacts with Thickveins and the endocytic machinery to attenuate retrograde BMP growth signaling during synaptic growth. Neuron 58:507-518. [PDF]
O’Connor-Giles, K.M. and J.B. Skeath. 2003. Numb inhibits membrane localization of Sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila. Dev. Cell 5:231-43. [PDF]


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Kate O'Connor-Giles Molecular regulation of synaptic growth E-mail: oconnorgiles@wisc.edu Research Strengths: Development, Plasticity and Repair Proper regulation of synaptic development and plasticity are fundamental to the function of neural circuits. Defects in synaptic growth are associated with a broad range of neurological disorders including developmental disorders; motor, cognitive and psychological impairments; and neurodegeneration. However, the molecular mechanisms regulating these processes are not well understood. Our research employs the Drosophila neuromuscular junction (NMJ) as a model system for dissecting the intrinsic and trans-synaptic mechanisms through which neurons and their targets coordinate the growth of synapses. We are currently investigating the role of Nervous wreck in the negative regulation of synaptic growth. Nervous wreck is a member of a conserved family of proteins implicated in severe cognitive and motor deficits. This work has revealed a novel presynaptic endocytic mechanism for regulating neuronal responsiveness to postsynaptically derived growth signals during NMJ development. To identify additional regulators of synaptic growth, we have conducted genetic screens that have uncovered a number of novel molecules with previously unknown roles in synaptogenesis. They encode a diverse set of proteins that likely function in multiple aspects of synaptic development and represent a rich resource for uncovering the molecular mechanisms that govern synaptic growth. Selected Publications: Babaoglan, A.B., K.M. O’Connor-Giles, H. Mistry, A. Schickedanz, B.A. Wilson, and J.B. Skeath. Sanpodo: a context-dependent activator and inhibitor of Notch signaling during asymmetric divisions. Submitted. O’Connor-Giles, K.M. and B. Ganetzky. 2008. Satellite Signaling at Synapses. Fly 2:259-61. O’Connor-Giles, K.M., L.L. Ho, and B. Ganetzky. 2008. Nervous wreck interacts with Thickveins and the endocytic machinery to attenuate retrograde BMP growth signaling during synaptic growth. Neuron 58:507-518. [PDF] O’Connor-Giles, K.M. and J.B. Skeath. 2003. Numb inhibits membrane localization of Sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila. Dev. Cell 5:231-43. [PDF]

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