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- Title
Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.
- Authors
Hutson, Mary R.; Keyte, Anna L.; Hernández-Morales, Miriam; Gibbs, Eric; Kupchinsky, Zachary A.; Argyridis, Ioannis; Erwin, Kyle N.; Pegram, Kelly; Kneifel, Margaret; Rosenberg, Paul B.; Matak, Pavle; Luke Xie; Grandl, Jörg; Davis, Erica E.; Katsanis, Nicholas; Chunlei Liu; Benner, Eric J.
- 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,we engineered 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.
- Subjects
HUMAN abnormalities; NEURAL crest; ELECTROMAGNETIC fields; RADIO frequency; FETAL development
- Publication
Science Signaling, 2017, Vol 10, Issue 500, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aal4055