The transcription factor MEF2C is required for craniofacial development
The transcription factor MEF2C is required for craniofacial development
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DOI：
10.1016/j.devcel.2007.03.007
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发表时间：
2007-04-01
影响因子：
11.8
通讯作者：
Black, Brian L.
中科院分区：
文献类型：
--
作者：
Verzi, Michael P.;Agarwal, Pooja;Black, Brian L.
MEF 2转录因子是肌肉发育的公认调节因子。我们已经发现了MEF 2C在神经嵴中的一个意想不到的作用，在神经嵴中，由于严重的颅面缺陷，组织特异性失活导致新生儿死亡。我们表明，MEF 2C是必需的Dlx 5，Dlx 6和Hand 2转录因子基因在鳃弓的表达，我们确定了一个鳃弓特异性增强子的Dlx 5/6位点，这是协同激活MEF 2C和Dlx 5，表明这些因素相互作用，以诱导转录。Mef 2c和Dlx 5/6也在遗传上相互作用。Dlx 5/6或Mef 2c杂合子小鼠在出生时是正常的，并存活至断奶。相比之下，Mef 2c和Dlx 5/6的杂合性导致腭发育缺陷和新生儿死亡。总而言之，本文提出的研究定义了颅面发育中MADS盒转录因子MEF 2C与同源结构域转录因子Dlx 5和Dlx 6之间的前馈转录回路。
MEF2 transcription factors are well-established regulators of muscle development. We have discovered an unanticipated role for MEF2C in the neural crest, where tissue-specific inactivation results in neonatal lethality due to severe craniofacial defects. We show that MEF2C is required for expression of the Dlx5, Dlx6, and Hand2 transcription factor genes in the branchial arches, and we identify a branchial arch-specific enhancer in the Dlx5/6 locus, which is activated synergistically by MEF2C and Dlx5, demonstrating that these factors interact to induce transcription. Mef2c and Dlx5/6 also interact genetically. Mice heterozygous for either Dlx5/6 or Mef2c are normal at birth and survive to weaning. By contrast, heterozygosity for both Mef2c and Dlx5/6 results in defective palate development and neonatal lethality. Taken together, the studies presented here define a feed-forward transcriptional circuit between the MADS-box transcription factor MEF2C and the homeodomain transcription factors Dlx5 and Dlx6 in craniofacial development.