Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis
Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis
复制标题
DOI：
10.1073/pnas.1208690109
复制
发表时间：
2012-11-13
影响因子：
11.1
通讯作者：
Tzahor, Eldad
中科院分区：
文献类型：
--
作者：
Harel, Itamar;Maezawa, Yoshiro;Tzahor, Eldad
对驱动脊椎动物器官发生的发育机制的探索为更深入地理解出生缺陷铺平了道路。在胚胎发生过程中，部分心脏和颅面肌起源于咽中胚层（PM）祖细胞。在这里，我们揭示了PM中表达的一组转录因子的分层调节网络，该网络启动心脏和颅面器官发生。在小鼠中，该网络的遗传扰动导致心脏和颅面肌肉缺陷，揭示了其成员之间强大的交叉调节。我们确定Lhx2在心脏和咽部肌肉发育过程中是一个先前未描述的参与者。Lhx2和Tcf21基因与Tbx1相互作用，Tbx1是digeorgge /velo-cardio-facial/22q11.2缺失综合征病因的主要决定因素。此外，在小鼠中敲除这些基因重现了该综合征的特定心脏特征。我们认为PM衍生的心脏发生和肌肉发生是网络特性，而不是PM个体成员特有的特性。这些发现为先天性缺陷的发育基础提供了新的线索。
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.