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

Publication ,  Journal Article
Hutson, MR; Keyte, AL; Hernández-Morales, M; Gibbs, E; Kupchinsky, ZA; Argyridis, I; Erwin, KN; Pegram, K; Kneifel, M; Rosenberg, PB; Matak, P ...
Published in: Sci Signal
October 10, 2017

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 cells was sufficient to induce these defects, we engineered iron-binding modifications 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.

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

October 10, 2017

Volume

10

Issue

500

Location

United States

Related Subject Headings

  • Zebrafish
  • TRPV Cation Channels
  • Pregnancy
  • Neural Crest
  • Mice, Inbred C57BL
  • Mice
  • Maternal-Fetal Exchange
  • Heart Failure
  • Fever
  • Female
 

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Chicago
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Hutson, M. R., Keyte, A. L., Hernández-Morales, M., Gibbs, E., Kupchinsky, Z. A., Argyridis, I., … Benner, E. J. (2017). Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects. Sci Signal, 10(500). https://doi.org/10.1126/scisignal.aal4055
Hutson, Mary R., Anna L. Keyte, Miriam Hernández-Morales, Eric Gibbs, Zachary A. Kupchinsky, Ioannis Argyridis, Kyle N. Erwin, et al. “Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.Sci Signal 10, no. 500 (October 10, 2017). https://doi.org/10.1126/scisignal.aal4055.
Hutson MR, Keyte AL, Hernández-Morales M, Gibbs E, Kupchinsky ZA, Argyridis I, et al. Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects. Sci Signal. 2017 Oct 10;10(500).
Hutson, Mary R., et al. “Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.Sci Signal, vol. 10, no. 500, Oct. 2017. Pubmed, doi:10.1126/scisignal.aal4055.
Hutson MR, Keyte AL, Hernández-Morales M, Gibbs E, Kupchinsky ZA, Argyridis I, Erwin KN, Pegram K, Kneifel M, Rosenberg PB, Matak P, Xie L, Grandl J, Davis EE, Katsanis N, Liu C, Benner EJ. Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects. Sci Signal. 2017 Oct 10;10(500).

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

October 10, 2017

Volume

10

Issue

500

Location

United States

Related Subject Headings

  • Zebrafish
  • TRPV Cation Channels
  • Pregnancy
  • Neural Crest
  • Mice, Inbred C57BL
  • Mice
  • Maternal-Fetal Exchange
  • Heart Failure
  • Fever
  • Female