| | |  | | | | Record from Web of Science® | | | | | | |
| Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum |
|
|
| Author(s): de la Pompa JL, Timmerman LA, Takimoto H, Yoshida H, Elia AJ, Samper E, Potter J, Wakeham A, Marengere L, Langille BL, Crabtree GR, Mak TW |
| Source: NATURE Volume: 392 Issue: 6672 Pages: 182-186 Published: MAR 12 1998 |
| Times Cited: 296 References: 24 |
| Abstract: In lymphocytes, the expression of early immune response genes is regulated by NF-AT transcription factors(1,2) which translocate to the nucleus after dephosphorylation by the Ca2+-dependent phosphatase, calcineurin(3). We report here that mice bearing a disruption in the NF-ATc gene fail to develop normal cardiac valves and septa and die of circulatory failure before day 14.5 of development. NF-ATc is first expressed in the heart at day 7.5, and is restricted to the endocardium, a specialized endothelium that gives rise to the valves and septum. Within the endocardium, specific inductive events appear to activate NF-ATc: it is localized to the nucleus only in endocardial cells that are adjacent to the interface with the cardiac jelly and myocardium, which are thought to give the inductive stimulus to the valve primordia(4). Treatment of wild-type embryos with FK506, a specific calcineurin inhibitor(5), prevents nuclear localization of NF-ATc. These data indicate that the Ca2+/calcineurin/NF-ATc signalling pathway is essential for normal cardiac valve and septum morphogenesis; hence, NF-ATc and its regulatory pathways are candidates for genetic defects underlying congenital human heart disease. |
| Document Type: Article |
| Language: English |
| Reprint Address: Mak, TW (reprint author), Univ Toronto, Ontario Canc Inst, Amgen Inst, 620 Univ Ave, Toronto, ON M5G 2C1 Canada |
Addresses:
1. Univ Toronto, Ontario Canc Inst, Amgen Inst, Toronto, ON M5G 2C1 Canada
2. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1 Canada
3. Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1 Canada
4. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Dev Biol, Stanford, CA 94305 USA
5. Univ Toronto, Dept Pathol, Toronto, ON M5S 1A8 Canada
6. Toronto Gen Div, Max Bell Res Ctr, Toronto, ON M5G 2C4 Canada |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: ZB349 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |