title: Neural progenitors organize in small-world networks to promote cell proliferation.
abstract: Coherent network activity among assemblies of interconnected cells is essential for diverse functions in the adult brain. However, cellular networks before formations of chemical synapses are poorly understood. Here, embryonic stem cell-derived neural progenitors were found to form networks exhibiting synchronous calcium ion (Ca(2+)) activity that stimulated cell proliferation. Immature neural cells established circuits that propagated electrical signals between neighboring cells, thereby activating voltage-gated Ca(2+) channels that triggered Ca(2+) oscillations. These network circuits were dependent on gap junctions, because blocking prevented electrotonic transmission both in vitro and in vivo. Inhibiting connexin 43 gap junctions abolished network activity, suppressed proliferation, and affected embryonic cortical layer formation. Cross-correlation analysis revealed highly correlated Ca(2+) activities in small-world networks that followed a scale-free topology. Graph theory predicts that such network designs are effective for biological systems. Taken together, these results demonstrate that immature cells in the developing brain organize in small-world networks that critically regulate neural progenitor proliferation.
authors.affiliation: Departments of Medical Biochemistry and Biophysics and Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Seth
authors.initials: S
authors.lastname: Malmersjö
authors.forename: Paola
authors.initials: P
authors.lastname: Rebellato
authors.forename: Erik
authors.initials: E
authors.lastname: Smedler
authors.forename: Henrike
authors.initials: H
authors.lastname: Planert
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kanatani
authors.forename: Isabel
authors.initials: I
authors.lastname: Liste
authors.forename: Evanthia
authors.initials: E
authors.lastname: Nanou
authors.forename: Hampus
authors.initials: H
authors.lastname: Sunner
authors.forename: Shaimaa
authors.initials: S
authors.lastname: Abdelhady
authors.forename: Songbai
authors.initials: S
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Andäng
authors.forename: Abdeljabbar
authors.initials: A
authors.lastname: El Manira
authors.forename: Gilad
authors.initials: G
authors.lastname: Silberberg
authors.forename: Ernest
authors.initials: E
authors.lastname: Arenas
authors.forename: Per
authors.initials: P
authors.lastname: Uhlén
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D049109:Cell Proliferation; D018031:Connexin 43 / Q000378:metabolism; D054351:Electrical Synapses / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008857:Microscopy, Interference; D008959:Models, Neurological; D009415:Nerve Net; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D020746:Calcium Channels, L-Type; D018031:Connexin 43; D034741:RNA, Small Interfering; D002118:Calcium