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

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.

Source: Signal Transduction Knowledge Environment - October 10, 2017 Category: Science Authors: Hutson, M. R., Keyte, A. L., Hernandez-Morales, M., Gibbs, E., Kupchinsky, Z. A., Argyridis, I., Erwin, K. N., Pegram, K., Kneifel, M., Rosenberg, P. B., Matak, P., Xie, L., Grandl, J., Davis, E. E., Katsanis, N., Liu, C., Benner, E. J. Tags: STKE Research Articles Source Type: news