Inactivation of TGFβ signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome
- Heiko Wurdak1,5,
- Lars M. Ittner2,5,
- Karl S. Lang3,
- Per Leveen4,
- Ueli Suter1,
- Jan A. Fischer2,
- Stefan Karlsson4,
- Walter Born2, and
- Lukas Sommer1,6
- 1Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, Zurich, CH-8093, Switzerland; 2Research Laboratory for Calcium Metabolism, University Hospital Balgrist, University of Zurich, Zurich, CH-8008, Switzerland; 3Institute of Experimental Immunology, University Hospital, University of Zurich, Zurich, CH-8091, Switzerland; 4Departments for Molecular Medicine and Gene Therapy, Lund University, Malmö, S-22184, Sweden
Abstract
Specific inactivation of TGFβ signaling in neural crest stem cells (NCSCs) results in cardiovascular defects and thymic, parathyroid, and craniofacial anomalies. All these malformations characterize DiGeorge syndrome, the most common microdeletion syndrome in humans. Consistent with a role of TGFβ in promoting non-neural lineages in NCSCs, mutant neural crest cells migrate into the pharyngeal apparatus but are unable to acquire non-neural cell fates. Moreover, in neural crest cells, TGFβ signaling is both sufficient and required for phosphorylation of CrkL, a signal adaptor protein implicated in the development of DiGeorge syndrome. Thus, TGFβ signal modulation in neural crest differentiation might play a crucial role in the etiology of DiGeorge syndrome.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.317405.
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↵5 These authors contributed equally to this work.
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↵6 Corresponding author. E-MAIL lukas.sommer{at}cell.biol.ethz.ch; FAX 41-1-633-10-69.
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- Accepted December 23, 2004.
- Received July 16, 2004.
- Cold Spring Harbor Laboratory Press
