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

TY - JOUR

T1 - Connexin45 modulates the proliferation of transit-amplifying precursor cells in the mouse subventricular zone

AU - Khodosevich, Konstantin

AU - Zuccotti, Annalisa

AU - Kreuzberg, Maria M

AU - Le Magueresse, Corentin

AU - Frank, Marina

AU - Willecke, Klaus

AU - Monyer, Hannah

PY - 2012/12/4

Y1 - 2012/12/4

N2 - 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.

AB - 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.

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors/metabolism

KW - Bromodeoxyuridine

KW - Cell Proliferation

KW - Connexins/metabolism

KW - Lateral Ventricles/cytology

KW - Mice

KW - Neural Stem Cells/physiology

KW - Neurogenesis/physiology

U2 - 10.1073/pnas.1217103109

DO - 10.1073/pnas.1217103109

M3 - Journal article

C2 - 23169657

SN - 0027-8424

VL - 109

SP - 20107

EP - 20112

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 49

ER -