Calcium Waves Propagate through Radial Glial Cells and Modulate Proliferation in the Developing Neocortex

Abstract

The majority of neurons in the adult neocortex are produced embryonically during a brief but intense period of neuronal proliferation. The radial glial cell, a transient embryonic cell type known for its crucial role in neuronal migration, has recently been shown to function as a neuronal progenitor cell and appears to produce most cortical pyramidal neurons. Radial glial cell modulation could thus affect neuron production, neuronal migration, and overall cortical architecture; however, signaling mechanisms among radial glia have not been studied directly. We demonstrate here that calcium waves propagate through radial glial cells in the proliferative cortical ventricular zone (VZ). Radial glial calcium waves occur spontaneously and require connexin hemichannels, P2Y1 ATP receptors, and intracellular IP3-mediated calcium release. Furthermore, we show that wave disruption decreases VZ proliferation during the peak of embryonic neurogenesis. Taken together, these results demonstrate a radial glial signaling mechanism that may regulate cortical neuronal production.

Activity-dependent neuron–glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development

“…For example, radial glial cells serve several functions during development, including migration of neurons and astrocytes and functioning as a progenitor cell pool for astrocytes (Goldman, 2003). Kriegstein and colleagues (Weissman et al, 2004) have demonstrated that radial glial cell migration and differentiation are regulated through purinergic signaling mediated by P 2 Y receptors. Progenitor cell proliferation from neurospheres can be regulated in an autocrine manner by pulsatile release of ATP from the progenitor cells themselves that decreases over several days in vitro (Lin et al, 2007).…”

Neuronal stem cells in the central nervous system and in human diseases

“…During mitosis, several studies have illustrated that RG cells remain in place without retraction from the pial surface throughout the whole cell cycle (Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2002Tamamaki et al, 2001;Weissman et al, 2004). Within the radial fiber of RG cells, the cytoplasm climbs toward the cell body with varicosities showing at intervals along the attenuated fiber (Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2002Tamamaki et al, 2001;Weissman et al, 2004).…”

Optic tectum morphogenesis: A step‐by‐step model based on the temporal–spatial organization of the cell proliferation. Significance of deterministic and stochastic components subsumed in the spatial organization

“…They also show that during the transition from the symmetric to asymmetric (neurogenic) divisions-when the G1 phase lengthens (Caviness et al, 1995;Takahashi et al, 1995)-the Ca waves dynamics significantly changes (see Fig. 7B in Weissman et al, 2004). These data lead to the postulation that Ca waves dynamically modulate the cell cycle within clusters of neighboring NEcs providing a temporal and spatial framework for an organized Each binary signal was divided into cph and cd halves.…”

“…Additionally, it has been reported that waves of intracellular Ca transients spontaneously appear and propagate through restricted spatial domains occupied by proliferating NEcs (Owens and Kriegstein, 1998;Noctor et al, 2004). Weissman et al (2004) have demonstrated that, in the developing rat neocortex, Ca waves are initiated by individuals NEc in late G1 or S phase by means of connexin hemichannels opening and ATP release; ATP acts on neighboring NEcs by activating the P2Y1 ATP receptor which, in turn, activates the IP3 signaling pathway leading to the production of Ca transients in adjacent NEcs. They show that Ca waves display a pattern of temporal clusters and that nearby waves often occur sequentially, in clusters radiating both spatially and temporally from one origin.…”

“…Given that mNEcs are frequently clumped into clusters of different sizes (Caviness et al, 1995;Cai et al, 1997aCai et al, , 2002Weissman et al, 2004;Rapacioli et al, 2011) and that such organization cannot be linearly characterized by estimating mean values of cluster size, inter-cluster interval length, or intra-cluster mNEcs density, the use of nonlinear methods appears as an alternative strategy to characterize its spatial organization. Three standardized methods of signal analyses were used to characterize the dynamics of the mNEc organization by estimating the scaling exponents of the signals derived from the mNEcs records (for references, see Lowen and Teich, 1995;Mazzeo et al, 2004).…”