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 novel 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. Mouse embryos were selected at E9.5, 10.5 and 11.5. We used Myf5Cre;RosaYFP in order to label all the myogenic lineage. Trunk (T) and Head (H) tissues were isolated, dispersed into a single cell suspension and FACS sorted for YFP+ population. Further analysis is described in Harel et al, PNAS (2012).

ORGANISM(S): Mus musculus

SUBMITTER: Eldad Tzahor 

PROVIDER: E-GEOD-42389 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress