Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, 97331, USA.
Cell Mol Life Sci. 2021 Jun;78(11):4921-4938. doi: 10.1007/s00018-021-03833-7. Epub 2021 Apr 12.
Homeobox genes encode sequence-specific transcription factors (SSTFs) that recognize specific DNA sequences and regulate organogenesis in all eukaryotes. They are essential in specifying spatial and temporal cell identity and as a result, their mutations often cause severe developmental defects. Pitx genes belong to the PRD class of the highly evolutionary conserved homeobox genes in all animals. Vertebrates possess three Pitx paralogs, Pitx1, Pitx2, and Pitx3 while non-vertebrates have only one Pitx gene. The ancient role of regulating left-right (LR) asymmetry is conserved while new functions emerge to afford more complex body plan and functionalities. In mouse, Pitx1 regulates hindlimb tissue patterning and pituitary development. Pitx2 is essential for the development of the oral cavity and abdominal wall while regulates the formation and symmetry of other organs including pituitary, heart, gut, lung among others by controlling growth control genes upon activation of the Wnt/ß-catenin signaling pathway. Pitx3 is essential for lens development and migration and survival of the dopaminergic neurons of the substantia nigra. Pitx gene mutations are linked to various congenital defects and cancers in humans. Pitx gene family has the potential to offer a new approach in regenerative medicine and aid in identifying new drug targets.
同源盒基因编码序列特异性转录因子（SSTFs），能够识别特定的 DNA 序列，并调节所有真核生物的器官发生。它们在确定空间和时间细胞身份方面至关重要，因此它们的突变通常会导致严重的发育缺陷。Pitx 基因属于 PRD 类高度进化保守的同源盒基因，存在于所有动物中。脊椎动物拥有三个 Pitx 同源基因，即 Pitx1、Pitx2 和 Pitx3，而非脊椎动物只有一个 Pitx 基因。调控左右（LR）不对称的古老作用是保守的，而新的功能则出现，以提供更复杂的身体结构和功能。在小鼠中，Pitx1 调节后肢组织模式和垂体发育。Pitx2 对于口腔和腹壁的发育至关重要，同时通过激活 Wnt/β-catenin 信号通路来控制生长控制基因，调节其他器官的形成和对称性，包括垂体、心脏、肠道、肺等。Pitx3 对于晶状体发育、迁移和黑质多巴胺能神经元的存活至关重要。Pitx 基因突变与人类的各种先天性缺陷和癌症有关。Pitx 基因家族有可能为再生医学提供新的方法，并有助于确定新的药物靶点。
