The effect of extrinsic Wnt/β-catenin signaling in Muller glia on retinal ganglion cell neurite growth
- 1 March 2020
- journal article
- research article
- Published by Wiley in Developmental Neurobiology
- Vol. 80 (3-4), 98-110
- https://doi.org/10.1002/dneu.22741
Abstract
Muller glia are the predominant glial cell type in the retina, and they structurally and metabolically support retinal neurons. Wnt/beta-catenin signaling pathways play essential roles in the central nervous system, including glial and neuronal differentiation, axonal growth, and neuronal regeneration. We previously demonstrated that Wnt signaling activation in retinal ganglion cells (RGC) induces axonal regeneration after injury. However, whether Wnt signaling within the adjacent Muller glia plays an axongenic role is not known. In this study, we characterized the effect of Wnt signaling in Muller glia on RGC neurite growth. Primary Muller glia and RGC cells were grown in transwell co-cultures and adenoviral constructs driving Wnt regulatory genes were used to activate and inhibit Wnt signaling specifically in primary Muller glia. Our results demonstrated that activation of Wnt signaling in Muller glia significantly increased RGC average neurite length and branch site number. In addition, the secretome of Muller glia after induction or inhibition of Wnt signaling was characterized using protein profiling of conditioned media by Q Exactive mass spectrometry. The Muller glia secretome after activation of Wnt signaling had distinct and more numerous proteins involved in regulation of axon extension, axon projection and cell adhesion. Furthermore, we showed highly redundant expression of Wnt signaling ligands in Muller glia and Frizzled receptors in RGCs and Muller glia. Therefore, this study provides new information about potential neurite growth promoting molecules in the Muller glia secretome, and identified Wnt-dependent target proteins that may mediate the axonal growth.Funding Information
- U.S. Department of Defense (WHX81‐16‐0715)
- National Eye Institute (EY014801, EY026546, EY027311)
- Research to Prevent Blindness (Unrestricted Grant)
This publication has 56 references indexed in Scilit:
- Wnt5a Controls Neurite Development in Olfactory Bulb InterneuronsASN Neuro, 2011
- Wnt5a Regulates Midbrain Dopaminergic Axon Growth and GuidancePLOS ONE, 2011
- Wnt/calcium signaling mediates axon growth and guidance in the developing corpus callosumDevelopmental Neurobiology, 2011
- Wnt2 Regulates Progenitor Proliferation in the Developing Ventral MidbrainOnline Journal of Public Health Informatics, 2010
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- TSP-1 Secreted by Bone Marrow Stromal Cells Contributes to Retinal Ganglion Cell Neurite Outgrowth and SurvivalPLOS ONE, 2008
- Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extensionExperimental Neurology, 2008
- Characterization of Wnt Signaling during Photoreceptor DegenerationInvestigative Ophthalmology & Visual Science, 2007
- The gene expression profile induced by Wnt 3a in NIH 3T3 fibroblastsJournal of Cell Communication and Signaling, 2007
- Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retinaDevelopmental Dynamics, 2003