Figure 2.

Schematic representation of the signaling pathways occurring during neural induction in the amphibian ectoderm cells (left panel) and in the ESCs (right panel). In both systems, neural commitment of naïve cells requires the activation of FGF/ERK signaling and the inhibition of BMP signaling by noggin and via the Erk-dependent phosphorylation of Smad1 at linker domain. An increase in intracellular Ca²⁺ concentration is also a common signal that drives embryonic cells toward the neural fate. However, the control of Ca²⁺ homeostasis differs between amphibian ectodermal cells and ESCs. While in amphibian, the main source of Ca²⁺ increase appears to rely on an influx through VOCCs (likely DHP-Ca²⁺ channels), ESCs do not express VOCC. In ESCs, the regulation of intracellular Ca²⁺ level depends on the activity of the SERCA2 pump, negatively regulated by neuronatin. Both cell types expressed TRP channels, probably TRPC, which could contribute to the Ca²⁺ signals. Gating of the VOCC in ectodermal cells could be due to membrane depolarization induced by the activation of TRPC. In ESCs, a direct link between intracellular Ca²⁺ increase and Erk phosphorylation has been established; in ectodermal cells the question of the amplification of the initial Ca²⁺ influx by the release of Ca²⁺ from the ER remains open. However, in both models Ca²⁺ signals participate in the inhibition of the BMP signaling pathway, either directly or indirectly via Erk-dependent phosphorylation of Smad1. Abbreviations: BMP, bone morphogenetic protein; BMPR, BMP receptor; ER, endoplasmic reticulum; ESC, embryonic stem cell; FGFR, fibroblast growth factor receptor; Nnat, neuronatin; Neural SC, neural stem cell; SERCA2, sarco/endoplasmic reticulum Ca²⁺-ATPase, isoform2; TRPC, class C transient potential receptor; VOCC, voltage-operated Ca²⁺ channels.