Developmental expression of the calcium release channels during early neurogenesis of the mouse cerebral cortex

Abstract

The developmental changes of intracellular calcium release channels of mouse neocortex were studied at the onset of neurogenesis, which occurs between embryonic days E11 and E17. The three main isoforms of the two families of intracellular calcium release channels, namely the inositol trisphosphate receptors (IP3R) and the ryanodine receptors (RyR), were detected by their transcripts in the cerebral hemispheres, as early as stage E11. The major isoforms of each family, IP3R-1 and RyR-2, were found at the protein level by Western blot analysis. Expression of these proteins increases progressively throughout brain development. Their localization in coronal sections of cortex has been observed by immunodetection from E12, and compared to the TuJ1 (anti-class III beta-tubulin antibody) neuronal specific labelling. The expression of both channels is greatly enhanced after E12, and both were seen to be present in most of the proliferative and neuronal cells of the slice. Between E12 and E13, there is a striking transition in the pattern of calcium release elicited by specific agonists of these channels, thimerosal for IP3R and caffeine for RyR. The signals induced by thimerosal were not zone-specific, while the observed calcium release signals induced by caffeine were predominantly restricted out of the ventricular zone. This zone-specific caffeine sensitivity is consistent with the main RyR localization immunodetected at E13. Our results indicate that there is a time lag of several days between the molecular detection of calcium release channels and their functional expression, around the time of neuronal differentiation. Altogether, they provide a molecular basis for analyzing the developmental modulation of calcium signals useful for neurogenesis progression.

An Ryr1 I4895T mutation abolishes Ca 2+ release channel function and delays development in homozygous offspring of a mutant mouse line

“…The delay becomes apparent from approximately E15.5-16 onward, even though Ryr1 transcripts are detected as early as E9.5 in somites (43) and E11.5 in the cerebral cortex (44). In our study, the only early sign of defective IT/IT embryo development was a mild and receding subcutaneous edema occurring at approximately E13.5 and suggesting possible abnormalities in vascular development.…”

Na + channel-mediated Ca 2+ entry leads to glutamate secretion in mouse neocortical preplate

“…We first aimed at identifying the mechanism between Na ϩ channel activation and Ca 2ϩ response. We previously showed that ryanodine receptor and inositol trisphosphate receptor are specifically present and functional in PP cells at E13 (15). Incubation of slices with 2 M thapsigargin (a Ca 2ϩ storedepleting agent) significantly decreases the number of PP cells that are activated by veratridine (30.3 Ϯ 5.7% vs. 58.0 Ϯ 6.8% in ACSF; n ϭ 15; P Ͻ 0.05; Fig.…”

“…Thus, in these cells, Na ϩ accumulated in response to veratridine is exchanged with external Ca 2ϩ , leading to Ca 2ϩ influx. Intracellular Ca 2ϩ stores are known to be functional in the neocortex at this stage (15). Thapsigargin partially blocks the veratridine effect, indicating that intracellular stores may contribute to signal amplification, probably by means of calciuminduced calcium release.…”

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

“…The expression of ER receptors for inositol trisphosphate (IP3R) and ryanodine (RyR) is precisely regulated in the cerebral cortex during embryonic development (Faure et al, 2001). We tested the effect of caffeine at concentrations that sensitize RyRs to resting calcium levels and promote calcium release through a calcium-induced calcium release (CICR) mechanism (Shirokova and Niggli, 2008).…”