Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Mar;59(2-3):124-34.
doi: 10.1016/j.ceca.2016.02.011. Epub 2016 Mar 15.

Regulation of neurogenesis by calcium signaling

Anna B Toth  1 , Andrew K Shum  1 , Murali Prakriya  2
Affiliations
Review

Regulation of neurogenesis by calcium signaling

Anna B Toth et al. Cell Calcium. 2016 Mar.

Abstract

Calcium (Ca(2+)) signaling has essential roles in the development of the nervous system from neural induction to the proliferation, migration, and differentiation of neural cells. Ca(2+) signaling pathways are shaped by interactions among metabotropic signaling cascades, intracellular Ca(2+) stores, ion channels, and a multitude of downstream effector proteins that activate specific genetic programs. The temporal and spatial dynamics of Ca(2+) signals are widely presumed to control the highly diverse yet specific genetic programs that establish the complex structures of the adult nervous system. Progress in the last two decades has led to significant advances in our understanding of the functional architecture of Ca(2+) signaling networks involved in neurogenesis. In this review, we assess the literature on the molecular and functional organization of Ca(2+) signaling networks in the developing nervous system and its impact on neural induction, gene expression, proliferation, migration, and differentiation. Particular emphasis is placed on the growing evidence for the involvement of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels in these processes.

Keywords: CRAC channel; Calcium; Neural development; Orai1; STIM1; Stem cells.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. Calcium signaling pathways in neural progenitor cells
Extracellular agonists (Ag) bind to cell surface receptors (R), including G protein-coupled receptors (GPCRs) such as mGluR, mAChR, and P2YR, and receptor tyrosine kinases (RTKs) such as Trk receptors and ErbB receptors. GPCRs activate phospholipase C (PLC)-β and RTKs activate PLCγ through G protein (G) or tyrosine kinase-coupled pathways (TK), respectively. PLC cleaves PIP2 to produce IP3, which mobilizes Ca2+ from ER stores via IP3R Ca2+ release channels. Upon store depletion, the luminal EF-hand domain of STIM1 senses the loss of ER [Ca2+], triggering STIM1 to oligomerize and translocate from the bulk ER to plasma membrane-ER junctions where it activates store-operated Ca2+ entry through CRAC channels. Voltage-gated Ca2+ channels (VOCCs) mediate Ca2+ influx in response to membrane depolarization. NMDA receptors (NMDAR) and nicotinic ACh receptors (nAChRs) are Ca2+-permeable channels that are activated by neurotransmitters glutamate and ACh, respectively. Transient receptor potential (TRP) channels are Ca2+-permeable channels that are activated by a wide variety of stimuli. These Ca2+ influx pathways contribute to a rise in cytosolic [Ca2+]i, which activates various Ca2+-dependent downstream gene expression pathways through regulation of transcription factors such as NFAT, CREB, NeuroD, and DREAM. Activation of these pathways has been linked to proliferation, migration, and differentiation of neural progenitor cells.
Fig. 2
Fig. 2. Schematic of the different stages of neurogenesis in the developing brain
Neurogenesis proceeds through several overlapping stages: proliferation, differentiation, migration, and maturation. The Ca2+ influx pathways expressed during these stages are indicated. Commonly used immunohistological markers for staging neurogenesis are also shown above.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Moreau M, Leclerc C. The choice between epidermal and neural fate: a matter of calcium. Int J Dev Biol. 2004;48:75–84. - PubMed
    1. Somasundaram A, Shum AK, McBride HJ, Kessler JA, Feske S, Miller RJ, Prakriya M. Store-operated CRAC channels regulate gene expression and proliferation in neural progenitor cells. J Neurosci. 2014;34:9107–9123. - PMC - PubMed
    1. Spitzer NC. Electrical activity in early neuronal development. Nature. 2006;444:707–712. - PubMed
    1. Zheng JQ, Poo MM. Calcium signaling in neuronal motility. Annu Rev Cell Dev Biol. 2007;23:375–404. - PubMed
    1. Rosenberg SS, Spitzer NC. Calcium signaling in neuronal development. Cold Spring Harb Perspect Biol. 2011;3:a004259. - PMC - PubMed

Publication types