From neuroepithelial cells to neurons: Changes in the physiological properties of neuroepithelial stem cells

The central nervous system, which includes the spinal cord, retina, and brain, is derived from the neural tube. The neural tube is formed of a sheet of cells called the neuroepithelium. During embryonic development, neuroepithelial cells function as neural stem cells: they renew themselves while undergoing interkinetic nuclear movements along the apico-basal axis during the cell cycle, and they produce postmitotic cells that function as newborn neurons. Neuroepithelial cells exhibit a robust increase in nucleoplasmic [Ca2+] in response to G protein-coupled receptor activation during S-phase when the nucleus is located in the basal region of the cell. This Ca2+ rise is caused by the release of Ca2+ from intracellular Ca2+ stores, and the Ca2+ release in turn activates Ca2+ entry from the extracellular space, which is called capacitative (or store-operated) Ca2+ entry. The Ca2+ release and store-operated Ca2+ entry are essential for DNA synthesis during S-phase. The activity of this store-operated Ca2+ signaling system declines in parallel with the decreasing proliferative activity of neuroepithelial cells. When exiting the cell cycle, the cells lose the apical process where gap junctions are located. Following the loss of gap junction coupling, the postmitotic cells show a high input resistance, which allows them to be readily depolarized. The Ca2+ response to the excitatory neurotransmitter glutamate appears and develops during neuronal differentiation. The glutamate-induced Ca2+ rise increases transiently during natural cell death (apoptosis). The rise in Ca2+ levels mediated by voltage-gated Ca2+ channels also develops during neuronal differentiation. Thus, when neuroepithelial cells differentiate into neurons, a transition from a store-operated system to a voltage-operated system occurs in the main Ca2+ signaling system. This transition may reflect a change in the mode of intercellular communication from a stored Ca2+-dependent mode to a plasma membrane potential-dependent mode.

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► Neuroepithelial cells act as neural stem cells during embryonic development.
► The main calcium signaling system changes during neurogenesis.
► Gap junction uncoupling functions as a signal for neuronal differentiation.