title: Pannexin 1 Differentially Affects Neural Precursor Cell Maintenance in the Ventricular Zone and Peri-Infarct Cortex.
abstract: We demonstrated previously that Pannexin 1 (Panx1), an ion and metabolite channel, promotes the growth and proliferation of ventricular zone (VZ) neural precursor cells (NPCs) in vitro. To investigate its role in vivo, we used floxed Panx1 mice in combination with viruses to delete Panx1 in VZ NPCs and to track numbers of Panx1-null and Panx1-expressing VZ NPCs over time. Two days after virus injection, Panx1-null cells were less abundant than Panx1-expressing cells, suggesting that Panx1 is required for the maintenance of VZ NPCs. We also investigated the effect of Panx1 deletion in VZ NPCs after focal cortical stroke via photothrombosis. Panx1 is essential for maintaining elevated VZ NPC numbers after stroke. In contrast, Panx1-null NPCs were more abundant than Panx1-expressing NPCs in the peri-infarct cortex. Together, these findings suggest that Panx1 plays an important role in NPC maintenance in the VZ niche in the naive and stroke brain and could be a key target for improving NPC survival in the peri-infarct cortex.
  
  
  CONCLUSIONS
  Here, we demonstrate that Pannexin 1 (Panx1) maintains a consistent population size of neural precursor cells in the ventricular zone, both in the healthy brain and in the context of stroke. In contrast, Panx1 appears to be detrimental to the survival of neural precursor cells that surround damaged cortical tissue in the stroke brain. This suggests that targeting Panx1 in the peri-infarct cortex, in combination with other therapies, could improve cell survival around the injury site.
authors.affiliation: Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8P 5C2, Canada.
authors.forename: Leigh E
authors.identifier: http://orcid.org/0000-0002-3235-4108
authors.initials: LE
authors.lastname: Wicki-Stordeur
authors.affiliation: Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8P 5C2, Canada.
authors.forename: Juan C
authors.identifier: http://orcid.org/0000-0002-8061-7128
authors.initials: JC
authors.lastname: Sanchez-Arias
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Jagroop
authors.initials: J
authors.lastname: Dhaliwal
authors.affiliation: Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8P 5C2, Canada.
authors.forename: Esther O
authors.initials: EO
authors.lastname: Carmona-Wagner
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida 33136, Vavilov Institute of General Genetics RAS, Moscow, Russian Federation 119333, and.
authors.forename: Valery I
authors.identifier: http://orcid.org/0000-0002-1568-6637
authors.initials: VI
authors.lastname: Shestopalov
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Diane C
authors.initials: DC
authors.lastname: Lagace
authors.affiliation: Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8P 5C2, Canada, Island Medical Program and Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada lswayne@uvic.ca.
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Swayne
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002544:Cerebral Infarction / Q000473:pathology*; D002552:Cerebral Ventricles / Q000166:cytology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D020521:Stroke / Q000150:complications
chemical_list: D017630:Connexins; D000089622:Doublecortin Domain Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C503631:Panx1 protein, mouse; D049452:Green Fluorescent Proteins; D053148:Caspase 3
keywords: neural precursor; pannexin; stroke
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