Connexin45 modulates the proliferation of transit-amplifying precursor cells in the mouse subventricular zone

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 49; pp. 20107 - 20112
• Main Authors: Khodosevich, Konstantin, Zuccotti, Annalisa, Kreuzberg, Maria M, Le Magueresse, Corentin, Frank, Marina, Willecke, Klaus, Monyer, Hannah
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04.12.2012; National Acad Sciences
• Subjects: Adenosine triphosphatase; adenosine triphosphate; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological Sciences; Brain; Bromodeoxyuridine; calcium; Cell adhesion & migration; Cell cycle; Cell growth; cell movement; Cell Proliferation; Connexins; Connexins - metabolism; embryogenesis; Embryonic stem cells; Lateral Ventricles - cytology; Lateral Ventricles - metabolism; Mammals; Mice; Neural stem cells; Neural Stem Cells - physiology; Neuroblasts; neurogenesis; Neurogenesis - physiology; Neurons; Retroviridae; Stem cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1217103109

Connexins have been implicated in the regulation of precursor cell migration and proliferation during embryonic development of the mammalian brain. However, their function in postnatal neurogenesis is unclear. Here we demonstrate that connexin (Cx) 45 is expressed in transit-amplifying cells and neuroblasts in the postnatal subventricular zone (SVZ) and modulated the proliferation of SVZ-derived precursor cells in vivo. Thus, overexpression of Cx45 by retroviral injections increased the proliferation of Mash-1–positive transit-amplifying precursor cells in the SVZ. Conversely, conditional deletion of Cx45 in precursor cells decreased proliferation. Finally, we established that Cx45 positively influences cell cycle reentry via ATP signaling that involves intracellular calcium stores and ERK1/2 signaling.