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.calcium signaling | neural networks | neural progenitor cells | spontaneous activity | stem cells

Neurons Forming Optic Glomeruli Compute Figure–Ground Discriminations inDrosophila

“…1C). Consistent with EM detection originating from the sum of local motion detector inputs (Single and Borst, 1998;Haag et al, 2004;Maisak et al, 2013), the EM STAF broadens with the wider figure that generates more motion energy ( Fig. 1Ci,Cii).…”

“…This indicates that our choice of a pruning threshold at p Ͻ 0.01 has little effect on the results reported. This procedure is similar to strategies that transform continuous measures of nearness or similarity into discrete ones to understand the topology of a neural code (Singh et al, 2008;Malmersjö et al, 2013). The graph layout as shown is calculated by the Fruchterman-Reingold algorithm (Fruchterman and Reingold, 1991).…”

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

“…We previously established that inhibition of GJIC by the rapid action of GR was associated with an inhibition of S-phase progression in cultured NPSCs (17). Our observation that transient pharmacologic inhibition of GJIC is also sufficient to reduce NPSC proliferation (17) was recently confirmed in cultured embryonic stem cell-derived neural progenitors and in embryonic neural progenitors isolated from the cerebral cortex (34). Recent studies in human hippocampal neural progenitor cells indicate that the antiproliferative properties of GCs are dependent upon at least one genomic GR target gene, Sgk-1 (19).…”

“…In summary, Cav-1 is a multifunctional regulator of GR action in NPSCs. Cav-1 influences both GR-dependent rapid changes in intercellular communication through gap junctions (17), which is required for the establishment of cerebral cortical architecture (34) and the GR transcriptome, including genes responsible for regulating NPSC proliferation. The wide variety of GR gene networks affected by Cav-1 also suggests that this novel regulator of receptor action could impact the ultimate fate and laminar position of cells derived from embryonic cerebral cortical NPSCs exposed prematurely to GCs during fetal development.…”

Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion

“…Ca 2+ imaging (Fig EV1D and E) and screening for PKCB knockout clones (immunostaining with PKCB antibody) were done using a fully automated fluorescence microscope (ImageXpress Micro XL, Molecular Devices), equipped with a Sola Light Engine (Lumencor), a Zyla 5.5 sCMOS camera (Andor), and a 20× 0.75 NA Plan Apo objective (Nikon). Cells for Ca 2+ imaging were loaded with the Ca 2+ ‐sensitive fluorescent indicator Fluo‐3/AM (Invitrogen) at 5 μM for 30 min in full growth media at 37°C and then imaged in extracellular buffer as described previously (Malmersjö et al , 2013). …”