Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Science. 2016 Jun 24;352(6293):1570-3. doi: 10.1126/science.aaf2729.
Neural crest populations along the embryonic body axis of vertebrates differ in developmental potential and fate, so that only the cranial neural crest can contribute to the craniofacial skeleton in vivo. We explored the regulatory program that imbues the cranial crest with its specialized features. Using axial-level specific enhancers to isolate and perform genome-wide profiling of the cranial versus trunk neural crest in chick embryos, we identified and characterized regulatory relationships between a set of cranial-specific transcription factors. Introducing components of this circuit into neural crest cells of the trunk alters their identity and endows these cells with the ability to give rise to chondroblasts in vivo. Our results demonstrate that gene regulatory circuits that support the formation of particular neural crest derivatives may be used to reprogram specific neural crest-derived cell types.
脊椎动物胚胎体轴上的神经嵴群体在发育潜力和命运上存在差异,因此只有颅神经嵴才能在体内对颅面骨骼做出贡献。我们探索了使颅神经嵴具有特殊特征的调控程序。我们使用轴向水平特异性增强子来分离和进行鸡胚颅神经嵴与躯干神经嵴的全基因组分析,鉴定并描述了一组颅神经嵴特异性转录因子之间的调控关系。将该回路的组成部分引入到躯干神经嵴细胞中,改变了它们的身份,并赋予这些细胞在体内产生成软骨细胞的能力。我们的结果表明,支持特定神经嵴衍生物形成的基因调控回路可用于重新编程特定的神经嵴衍生细胞类型。