Cross-regulation of Connexin43 and β-catenin influences differentiation of human neural progenitor cells.
Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ) protein and it is strongly associated with the regulation of cell cycle progression. Emerging roles for Cx43 in cell adhesion and migration during neural differentiation have also been recently recognized, and this has emphasized the involvement of Cx43 in different physiological process beyond its role as a GJ protein. In this study, we explore the function of Cx43 in the differentiation of human neural progenitor cells (hNPCs) using viral vectors that mediate the overexpression or knockdown of the protein. Results showed that in the absence of this protein fetal cortex-derived hNPCs differentiated toward a neuronal phenotype at expenses of a glial phenotype. Furthermore, the silencing of Cx43 did not affect hNPC proliferation rate or numbers of apoptotic cells. The increase in the number of neurons was not recapitulated when GJ intercellular communications were pharmacologically blocked, and this suggested that Cx43 was influencing hNPCs differentiation with a GJ-independent effect. In addition, Cx43 knockdown significantly increased β-catenin signaling, which has been shown to regulate the transcription of pro-neuronal genes during embryonic neural development. Our results add further support to the hypothesis that Cx43 protein itself regulates key signaling pathways during development and neurogenesis beyond its role as GJ protein.
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
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F
Rinaldi
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
E M
EM
Hartfield
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
L A
LA
Crompton
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
J L
JL
Badger
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
C P
CP
Glover
Brain Repair Group, School of Biosciences, Life Science Building, University of Cardiff, Cardiff, UK.
C M
CM
Kelly
1] Brain Repair Group, School of Biosciences, Life Science Building, University of Cardiff, Cardiff, UK [2] Department of Neurology, School of Medicine, University of Cardiff, Cardiff, UK.
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AE
Rosser
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
J B
JB
Uney
Stem Cells and Neuroregeneration Research Group, School of Clinical Sciences, Medical Sciences Building, University Walk, University of Bristol, Bristol, UK.
M A
MA
Caldwell
D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D018031:Connexin 43; D051176:beta Catenin