Abstract
Calcium fluxes have been implicated in the specification of the vertebrate embryonic nervous system for some time, but how these fluxes are regulated and how they relate to the rest of the neural induction cascade is unknown. Here we describe Calfacilitin, a transmembrane calcium channel facilitator that increases calcium flux by generating a larger window current and slowing inactivation of the L-type CaV1.2 channel. Calfacilitin binds to this channel and is co-expressed with it in the embryo. Regulation of intracellular calcium by Calfacilitin is required for expression of the neural plate specifiers Geminin and Sox2 and for neural plate formation. Loss-of-function of Calfacilitin can be rescued by ionomycin, which increases intracellular calcium. Our results elucidate the role of calcium fluxes in early neural development and uncover a new factor in the modulation of calcium signalling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Patterning / drug effects
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Body Patterning / genetics
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Calcium / metabolism
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Calcium Channels / metabolism*
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Calcium Channels, L-Type / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / genetics
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Chick Embryo
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Geminin / metabolism
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Gene Expression Regulation, Developmental / drug effects
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Germ Layers / cytology
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Germ Layers / drug effects
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Germ Layers / metabolism
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HEK293 Cells
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Humans
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Intracellular Space / drug effects
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Intracellular Space / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Morpholinos / pharmacology
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Neural Plate / drug effects
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Neural Plate / embryology*
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Neural Plate / metabolism*
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Quail
Substances
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Calcium Channels
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Calcium Channels, L-Type
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Geminin
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L-type calcium channel alpha(1C)
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Membrane Proteins
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Morpholinos
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Calcium