期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 46, 页码 18839-18844出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1208690109
关键词
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资金
- European Research Council
- Israel Science Foundation
- United States-Israel Binational Science Foundation
- German Israeli Foundation
- Association Francaise Contre les Myopathies
- Kirk Center for Childhood Cancer and Immunological Disorders
- Jeanne and Joseph Nissim Foundation for Life Sciences Research
- National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR054406]
- Institute Of Cancer Research
- Ministry of Science and Innovation [BFU2011-22928]
- Jack Gitlitz Estate
The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.
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