title: Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons.
abstract: The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons.
authors.affiliation: Department of Anatomy and Neurobiology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19129.
authors.forename: Tanuja T
authors.initials: TT
authors.lastname: Merianda
authors.affiliation: Department of Anatomy and Neurobiology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19129.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biological Sciences, University of South Carolina , Columbia, South Carolina 29208.
authors.forename: Ashley L
authors.identifier: 0000-0001-7611-0810
authors.initials: AL
authors.lastname: Kalinski
authors.affiliation: Department of Biological Sciences, University of South Carolina , Columbia, South Carolina 29208.
authors.forename: Pabitra K
authors.identifier: 0000-0002-1076-9409
authors.initials: PK
authors.lastname: Sahoo
authors.affiliation: Department of Anatomy and Neurobiology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19129.
authors.forename: Itzhak
authors.identifier: 0000-0003-3187-8740
authors.initials: I
authors.lastname: Fischer
authors.affiliation: Department of Biological Sciences, University of South Carolina , Columbia, South Carolina 29208.
authors.forename: Jeffery L
authors.identifier: 0000-0001-7875-6682
authors.initials: JL
authors.lastname: Twiss
mesh_terms: D000199:Actins / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005260:Female; D019922:GAP-43 Protein / Q000008:administration & dosage / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D064451:Hepcidins / Q000378:metabolism; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D000071446:Neuronal Outgrowth / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D000199:Actins; D017077:Culture Media, Conditioned; D019922:GAP-43 Protein; C578703:Hamp protein, rat; D064451:Hepcidins; D012333:RNA, Messenger
keywords: axonal transport; glial restricted progenitor; mRNA localization; neural restricted progenitor; stem cell