Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis
Publication Date
2012-11-13ICR Author
Author
Harel, I
Maezawa, Y
Avraham, R
Rinon, A
Ma, H-Y
Cross, JW
Leviatan, N
Hegesh, J
Roy, A
Jacob-Hirsch, J
Rechavi, G
Carvajal, J
Tole, S
Kioussi, C
Quaggin, S
Tzahor, E
Type
Journal Article
Metadata
Show full item recordAbstract
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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Version of record
Research team
Molecular Embryology
Language
English
License start date
2012-11-13
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 pp. 18839 - 18844
Publisher
NATL ACAD SCIENCES