Table of Contents
Developmental Biology Journal
Volume 2013, Article ID 131529, 8 pages
Research Article

Targeted Disruption of Calcium/NFAT Signaling Reveals a Left-Right Determination Disorder in the Pharyngeal Arch Artery

Laboratory for Occupational Safety and Health, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita 565-8565, Japan

Received 7 December 2012; Accepted 18 February 2013

Academic Editor: Tetsuya Kojima

Copyright © 2013 Yukihisa Miyachi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


An immunosuppressant was injected into pregnant mice in order to investigate whether the immune response is involved in differentiation during embryonic development. Injection of 3 mg/kg of FK506, an inhibitor of calcineurin, early in the organogenesis period increased the penetrance of right aortic arch formation by 32% compared with saline injection. Immunosuppressants such as FTY720 and rapamycin did not affect left/right (L/R) determination. FK506 is known to work by restricting NFAT (nuclear factor activated T-cell) dephosphorylation. An L/R determination disorder in cardiac outflows appeared when an NFATc4 siRNA was directly injected into the amniotic fluid. As for the mechanism, Pitx2, which is normally expressed on the left-hand side, was found to be expressed also on the right-hand side. Furthermore, it turned out that administration of FK506 also prevented the dephosphorylation of NSFL1 cofactor p47. When an siRNA targeting p47 was introduced into the amniotic fluid of FK506-treated fetuses, both of the dorsal arteries—which should normally become one—remained. These findings indicate that the mother's immune system contributes not only to self defense, but also to remodeling processes in fetal morphogenesis.