Spontaneous calcium transients are required for neuronal differentiation of murine neural crest

Marc B. Carey, Steven G. Matsumoto

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

We have shown that cultured mouse neural crest (NC) cells exhibit transient increases in intracellular calcium. Up to 50% of the cultured NC- derived cells exhibited calcium transients during the period of neuronal differentiation. As neurogenic activity declined, so did the percentage of active NC-derived cells and their calcium spiking frequency. The decrease in calcium transient activity correlated with a decreased sensitivity to thimerosal, which sensitizes inositol 1,4,5-triphosphate receptors. Thimerosal increased the frequency of oscillations in active NC-derived cells and induced them in a subpopulation of quiescent cells. As neurogenesis ended, NC-derived cells became nonresponsive to thimerosal. Using the expression of time-dependent neuronal traits, we determined that neurons exhibited spontaneous calcium transients as early as a neuronal phenotype could be detected and continued through the acquisition of caffeine sensitivity, soon after which calcium transient activity stopped. A subpopulation of nonneuronal NC-derived cells exhibited calcium transient activity within the same time frame as neurogenesis in culture. Exposing NC- derived cells to 20 mM Mg2+ blocked calcium transient activity and reduced neuronal number without affecting the survival of differentiated neurons. Using lineage-tracing analysis, we found that 50% of active NC-derived cells gave rise to clones containing neurons, while inactive cells did not. We hypothesize that calcium transient activity establishes a neuronal competence for undifferentiated NC cells.

Original languageEnglish (US)
Pages (from-to)298-313
Number of pages16
JournalDevelopmental Biology
Volume215
Issue number2
DOIs
StatePublished - Nov 15 1999

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Keywords

  • Cell autonomous
  • Differentiation
  • IP
  • Lineage analysis
  • Neuronal progenitor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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