Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis

Itamar Harel, Yoshiro Maezawa, Roi Avraham, Ariel Rinon, Hsiao Yen Ma, Joe W. Cross, Noam Leviatan, Julius Hegesh, Achira Roy, Jasmine Jacob-Hirsch, Gideon Rechavi, Jaime Carvajal, Shubha Tole, Chrissa Kioussi, Susan Quaggin, Eldad Tzahor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18839-18844
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number46
DOIs
StatePublished - Nov 13 2012

ASJC Scopus subject areas

  • General

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