Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects

Mary R. Hutson, Anna L. Keyte, Miriam Hernández-Morales, Eric Gibbs, Zachary A. Kupchinsky, Ioannis Argyridis, Kyle N. Erwin, Kelly Pegram, Margaret Kneifel, Paul B. Rosenberg, Pavle Matak, Luke Xie, Jörg Grandl, Erica Ellen Davis, Elias Nicholas Katsanis, Chunlei Liu, Eric J. Benner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors.Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk tissues. We report that two heat-activated transient receptor potential (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during critical windows of heart and face development. TRPV1 antagonists protected against the development of hyperthermia-induced defects in chick embryos. Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia-induced birth defects in chick and zebrafish embryos. To test whether transient TRPV channel permeability in neural crest cellswas sufficient to induce these defects, weengineered iron-bindingmodifications to TRPV1 and TRPV4 that enabled remote and noninvasive activation of these channels in specific cellular locations and at specific developmental times in chick embryos with radio-frequency electromagnetic fields. Transient stimulation of radio frequency-controlled TRP channels in neural crest cells replicated fever-associated defects in developing chick embryos. Our data provide a previously undescribed mechanism for congenital defects, whereby hyperthermia activates ion channels that negatively affect fetal development.

Original languageEnglish (US)
Article numbereaal4055
JournalScience Signaling
Volume10
Issue number500
DOIs
StatePublished - Oct 10 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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