Kropp Peter A, Gannon Maureen
Department of Molecular Physiology and Biophysicsm Vanderbilt University, Nashville, TN; Program in Developmental Biology, Vanderbilt University, Nashville, TN.
Department of Molecular Physiology and Biophysicsm Vanderbilt University, Nashville, TN; Department of Medicine, Vanderbilt University, Nashville, TN; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN; Program in Developmental Biology, Vanderbilt University, Nashville, TN; Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA.
Trends Dev Biol. 2016;9:43-57.
Developmental processes are remarkably well conserved among species, and among the most highly conserved developmental regulators are transcription factor families. The Onecut transcription factor family consists of three members known for their single "cut" DNA-binding domain and an aberrant homeodomain. The three members of the Onecut family are highly conserved from to humans and have significant roles in regulating the development of diverse tissues derived from the ectoderm or endoderm, where they activate a number of gene families. Of note, the genetic interaction between Onecut family members and genes appears to be essential in multiple tissues for proper specification and development of unique cell types. This review highlights the importance of the Onecut factors in cell fate specification and organogenesis, highlighting their role in vertebrates, and discusses their role in the maintenance of cell fate and prevention of disease. We cover the essential spatial and temporal control of Onecut factor expression and how this tight regulation is required for proper specification and subsequent terminal differentiation of multiple tissue types including those within the retina, central nervous system, liver and pancreas. Beyond development, Onecut factors perform necessary functions in mature cell types; their misregulation can contribute to diseases such as pancreatic cancer. Given the importance of this family of transcription factors in development and disease, their consideration in essential transcription factor networks is underappreciated.
发育过程在物种间显著保守，而转录因子家族是最为保守的发育调节因子之一。Onecut转录因子家族由三个成员组成，它们以单一的“切割”DNA结合结构域和异常的同源结构域而闻名。Onecut家族的三个成员从[具体物种]到人类都高度保守，在调节源自外胚层或内胚层的多种组织的发育中发挥着重要作用，它们在这些组织中激活许多基因家族。值得注意的是，Onecut家族成员与[具体基因]之间的遗传相互作用在多种组织中对于独特细胞类型的正确特化和发育似乎至关重要。本综述强调了Onecut因子在细胞命运特化和器官发生中的重要性，突出了它们在脊椎动物中的作用，并讨论了它们在维持细胞命运和预防疾病中的作用。我们阐述了Onecut因子表达在空间和时间上的必要控制，以及这种严格调控对于包括视网膜、中枢神经系统、肝脏和胰腺在内的多种组织类型的正确特化和随后的终末分化是如何必需的。在发育之外，Onecut因子在成熟细胞类型中发挥着必要功能；它们的失调会导致诸如胰腺癌等疾病。鉴于这个转录因子家族在发育和疾病中的重要性，它们在重要转录因子网络中的作用尚未得到充分认识。
