title: EGCG stabilizes growth cone filopodia and impairs retinal ganglion cell axon guidance.
abstract: Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain.
  
  
  
  EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid-diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior.
  
  
  
  We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667-677, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychology, Mount Royal University, Calgary, Alberta.
authors.forename: Karen
authors.initials: K
authors.lastname: Atkinson-Leadbeater
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Hehr
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta.
authors.forename: Jill
authors.initials: J
authors.lastname: Johnston
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bertolesi
authors.affiliation: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta.
authors.forename: Sarah
authors.initials: S
authors.lastname: McFarlane
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000187:drug effects; D001369:Axons / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004027:Diencephalon / Q000166:cytology / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D005260:Female; D020439:Growth Cones / Q000187:drug effects*; D006801:Humans; D017403:In Situ Hybridization; D055495:Neurogenesis / Q000187:drug effects; D011554:Pseudopodia / Q000187:drug effects*; D012160:Retina / Q000166:cytology / Q000187:drug effects; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects*; D014981:Xenopus
chemical_list: D006063:Chorionic Gonadotropin; D002392:Catechin; C045651:epigallocatechin gallate
keywords: F-actin; Mical; Xenopus; antioxidant; green tea extract; optic tract