Wnt family proteins play important roles in axon pathfinding and target selection during the wiring of the nervous system. They provide directional information for the navigating growth cones and either attract or repel axons by signaling through specific receptors and signaling ways. Atypical PKC (aPKC), a key component of apical-basal (A-B) polarity signaling in neural epithelial cells, mediates Wnt attraction and anterior-directed turning of spinal cord commissural axons after midline crossing, a model system for axon guidance studies. Preliminary results showed that core Wnt/planar-cellpolarity (Wnt/PCP) signaling components are also required for A-P guidance of commissural axons. The renewal proposal will investigate whether the two epithelial polarity-signaling pathways are involved in mediating Wnt signaling in A-P axon guidance and, if so, how the two pathways are integrated. The cellular mechanisms of growth cone guidance, particularly membrane trafficking and its relationship with microtubule dynamics, are currently understudied. This proposal will tackle the role of membrane trafficking and microtubule dynamics in growth cone guidance. In addition, the role of Wnt signaling in brain wiring and formation of functional circuits are still poorly known. This proposal will use the brainstem monoaminergic axons as an inroad to study how Wnts organize distinct brain circuits to control behavior.
Aim 1 : Characterization of PCP and aPKC/A-B polarity signaling components in Wnt signaling and A-P axon guidance.
Aim 2 : Cellular mechanisms of PCP and PKCz/A-B polarity signaling pathways in growth cone guidance.
Aim 3 : Role of Wnt signaling in brain circuit wiring. Wnts are large family of proteins (19 members) with three diverse classes of receptors, the Frizzleds (10 members), Ryk and ROR2, all widely expressed in the nervous system. The Wnt guidance system likely plays major roles in wiring. The Wnt guidance system is re-induced after injury in adult spinal cord and regulates adult corticospinal tract axon regeneration. The proposed studies will enhance the understanding of the molecular and cellular mechanisms of CNS axon wiring in development as well as provide tools for nervous system regeneration following traumatic injury and degeneration of the CNS.
The Wnt guidance system plays important roles in central nervous system wiring and is re-induced after injury in adult spinal cord and regulates adult corticospinal tract axon regeneration. The proposed studies will enhance the understanding of the molecular and cellular mechanisms of CNS axon wiring in development as well as provide tools for nervous system regeneration following traumatic injury and degeneration of the CNS.
|Huang, Ming; Cheng, Gen; Tan, Han et al. (2017) Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors. Exp Neurol 295:66-76|
|Thakar, Sonal; Wang, Liqing; Yu, Ting et al. (2017) Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation. Proc Natl Acad Sci U S A 114:E610-E618|
|Ponsetto, Joseph L; Bezryadina, Anna; Wei, Feifei et al. (2017) Experimental Demonstration of Localized Plasmonic Structured Illumination Microscopy. ACS Nano 11:5344-5350|
|Li, Zezhi; Wang, Zuowei; Zhang, Chen et al. (2017) Reduced ENA78 levels as novel biomarker for major depressive disorder and venlafaxine efficiency: Result from a prospective longitudinal study. Psychoneuroendocrinology 81:113-121|
|Hollis 2nd, Edmund R; Ishiko, Nao; Yu, Ting et al. (2016) Ryk controls remapping of motor cortex during functional recovery after spinal cord injury. Nat Neurosci 19:697-705|
|Hollis 2nd, Edmund R; Ishiko, Nao; Pessian, Maysam et al. (2015) Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery. Nat Commun 6:6079|
|Hollis 2nd, Edmund R; Ishiko, Nao; Tolentino, Kristine et al. (2015) A novel and robust conditioning lesion induced by ethidium bromide. Exp Neurol 265:30-9|
|Lemmon, Vance P; Ferguson, Adam R; Popovich, Phillip G et al. (2014) Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments. J Neurotrauma 31:1354-61|
|Zou, Yimin; Salinas, Patricia (2014) Introduction: Wnt signaling mechanisms in development and disease. Dev Neurobiol 74:757-8|
|Onishi, Keisuke; Hollis, Edmund; Zou, Yimin (2014) Axon guidance and injury-lessons from Wnts and Wnt signaling. Curr Opin Neurobiol 27:232-40|
Showing the most recent 10 out of 26 publications