Christopher C. Quinn
Assistant Professor
Cell Biology, Developmental Genetics and Neuroscience


Christopher C. QuinnB.A., Rutgers University 1996
Ph.D., Yale University 2001
Postdoctoral, UMDNJ-RWJMS 2001-2006

Office: Lapham N413
Phone: 414-229-2602
FAX: 414-229-3926
Email: quinnc@uwm.edu
Vitae:

Research Interests

Quinn-1
Figure 1. Polarization of MIG-10/lamellipodin in response to guidance cues. (a) UNC-6/netrin is secreted from sources ventral to the HSN neuron. (b) MIG-10::YFP localization in the C. elegans HSN neuron during the response to UNC-6/netrin. (c-f) Asymmetric localization of MIG-10::GFP in the growth cone of a cultured cortical neuron double stained for F-actin and microtubules. Scale bars 5µm. . Figure adapted with permission from Trends in Cell Biology, 18:597-603.

Our lab is interested in the question of how neural circuits are formed during development. Failures in this process may underlie mental and neurological disorders such as Autism and Down Syndrome. In addition, it is widely believed that an understanding of the mechanisms that control neural circuit formation will lead to the development of therapies to promote regeneration after neural injury.

We are currently focusing on axon guidance, a key step in the formation of neural circuits. Axon guidance involves the navigation of axons through the developing nervous system to reach their synaptic targets. This process is mediated by the growth cone, a structure that sits at the tip of growing axons. The growth cone steers to its target by making a series of attractive and repulsive responses to extracellular guidance cues. Previous studies have been successful in identifying several axon guidance cues and receptors. However, much less is known about the intracellular machinery that enables the growth cone to sense and respond to directional information. An important, yet poorly understood, part of this response involves the establishment of asymmetry within the growth cone. To learn about how asymmetry is established, we are taking advantage of the powerful genetic analysis that is possible with the model organism C. elegans, and complementing this with biochemical and cell culture experiments.

We have recently identified MIG-10/lamellipodin as an intracellular scaffolding protein that is required for guidance and is asymmetrically localized within the neuron as it responds to extracellular guidance cues (See Figure 1). We have found that MIG-10 is asymmetrically recruited by an interaction with the Rac GTPase, a component of a highly conserved direction-sensing module (See Figure 2). We are currently taking advantage of these findings to build our understanding of how asymmetry is established within the growth cone.

Model for asymmetric localization of MIG-10/lamellipodin in a growth cone 
Figure 2. Model for asymmetric localization of MIG-10/lamellipodin in a growth cone during axon guidance. (a) In the absence of an UNC-6/netrin gradient, the UNC-40/DCC receptor is distributed uniformly. (b) In the presence of a gradient of UNC-6, UNC-40 becomes polarized to the side of the growth cone closest to the source of UNC-6. This asymmetric localization of UNC-40 would cause asymmetric activation of Rac and asymmetric localization of PtdIns(3,4)P2. MIG-10 binds to activated Rac and PtdIns(3,4)P2, thus, causing asymmetric localization of MIG-10. Asymmetric localization of MIG-10 causes asymmetric actin-based protrusive activity, thereby causing growth-cone turning. Figure adapted with permission from Trends in Cell Biology, 18:597-603.

Selected Publications

  1. Xu Y, Quinn CC (2012) MIG-10 functions with ABI-1 to mediate the UNC-6 and SLT-1 axon guidance signaling pathways. PLoS Genetics 8(11): e1003054.
  2. Xu Y, Ren XC, Quinn CC, Wasdsworth WG. (2011) Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis elegans. Genetics 189:899-906.
  3. Quinn CC and Wadsworth WG (2008) Axon Guidance: Asymmetric signaling orients polarized outgrowth. Trends in Cell Biology 18:597-603.
  4. Quinn CC, Pfeil DS, Wadsworth WG (2008) Ced-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin. Current Biology 18:808-13.
  5. Quinn CC and Wadsworth WG (2006) Axon Guidance: Ephrins at WRK on the Midline. Current Biology 16:R954-5.
  6. Quinn CC, Pfeil DS, Chen E, Stovall EL, Harden MV, Gavin MK, Forrester WC, Ryder EF, Soto MC, Wadsworth WG (2006) UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin. Current Biology 16:845-853.
  7. Quinn CC, Chen E, Kinjo TG, Kelly G, Bell AW, Elliott RC, McPherson PS, Hockfield S (2003) TUC-4b, a novel TUC family variant, regulates neurite outgrowth and associates with vesicles in the growth cone. Journal of Neuroscience 23:2815-2823.
  8. Benvenuti S, Cramer R, Quinn CC, Bruce J, Zvelebil M, Corless S, Bond J, Yang A, Hockfield S, Burlingame AL, Waterfield MD, Jat PS (2002) Differential proteome analysis of replicative senescence in rat embryo fibroblasts. Mol. Cell. Proteomics. 1:280-292.
  9. Wasiak S, Quinn CC, Ritter B, de Heuvel E, Baranes D, Plomann M, McPherson PS (2001) The Ras/Rac guanine nucleotide exchange factor mammalian Son-of-sevenless interacts with PACSIN1/syndapin I, a regulator of endocytosis and the actin cytoskeleton. Journal of Biological Chemistry 276:26622-26628.
  10. Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS (2001) Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nature Cell Biology 10:927-932.
  11. Tong XK, Hussain NK, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn CC, Olson MF, Marais R, Baranes D, Kay BK, McPherson PS. (2000). The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain. EMBO Journal 19: 1263-1271.
  12. Quinn CC, Gray GE, Hockfield S. (1999). A family of proteins implicated in axon guidance and outgrowth. Journal of Neurobiology 41:158-164.