title: Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.
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.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Harel
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Roi
authors.initials: R
authors.lastname: Avraham
authors.forename: Ariel
authors.initials: A
authors.lastname: Rinon
authors.forename: Hsiao-Yen
authors.initials: HY
authors.lastname: Ma
authors.forename: Joe W
authors.initials: JW
authors.lastname: Cross
authors.forename: Noam
authors.initials: N
authors.lastname: Leviatan
authors.forename: Julius
authors.initials: J
authors.lastname: Hegesh
authors.forename: Achira
authors.initials: A
authors.lastname: Roy
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Jaime
authors.initials: J
authors.lastname: Carvajal
authors.forename: Shubha
authors.initials: S
authors.lastname: Tole
authors.forename: Chrissa
authors.initials: C
authors.lastname: Kioussi
authors.forename: Susan
authors.initials: S
authors.lastname: Quaggin
authors.forename: Eldad
authors.initials: E
authors.lastname: Tzahor
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology*; D006257:Head / Q000196:embryology*; D006321:Heart / Q000196:embryology*; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000196:embryology*; D009206:Myocardium
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C454301:Lnx2 protein, mouse; C112923:Tcf21 protein, mouse