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PMID: 15741317 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inactivation of TGFbeta signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome.

Genes & development ·Vol. 19 ·No. 5 ·2005-03-01 ·Pages 530-5

Wurdak H, Ittner LM, Lang KS, Leveen P, Suter U, Fischer JA, Karlsson S, Born W, Sommer L

Abstract

Specific inactivation of TGFbeta 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 TGFbeta 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, TGFbeta signaling is both sufficient and required for phosphorylation of CrkL, a signal adaptor protein implicated in the development of DiGeorge syndrome. Thus, TGFbeta signal modulation in neural crest differentiation might play a crucial role in the etiology of DiGeorge syndrome.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Cell Differentiation/genetics,physiology DiGeorge Syndrome/etiology,genetics,metabolism Gene Expression Regulation, Developmental/genetics,physiology Humans Mice Mice, Knockout Neural Crest/cytology,physiology Nuclear Proteins/genetics,metabolism Phosphorylation Signal Transduction/genetics,physiology Stem Cells/physiology Transforming Growth Factor beta/metabolism
Chemicals
Adaptor Proteins, Signal Transducing CRKL protein Nuclear Proteins Transforming Growth Factor beta
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wurdak Heiko
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, Zurich, CH-8093, Switzerland.
Ittner Lars M
Lang Karl S
Leveen Per
Suter Ueli
Fischer Jan A
Karlsson Stefan
Born Walter
Sommer Lukas
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.317405
Published
2005-03-01
Pages
530-5
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC551573
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.317405 PMC Full Text View journal details
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