Université de Paris, Institut Cochin, INSERM, CNRS, 75014, Paris, France.
Université de Paris, Institut Cochin, INSERM, CNRS, 75014, Paris, France.
Semin Cell Dev Biol. 2020 Aug;104:51-64. doi: 10.1016/j.semcdb.2020.03.003. Epub 2020 Apr 1.
SIX homeoproteins were first described in Drosophila, where they participate in the Pax-Six-Eya-Dach (PSED) network with eyeless, eyes absent and dachsund to drive synergistically eye development through genetic and biochemical interactions. The role of the PSED network and SIX proteins in muscle formation in vertebrates was subsequently identified. Evolutionary conserved interactions with EYA and DACH proteins underlie the activity of SIX transcriptional complexes (STC) both during embryogenesis and in adult myofibers. Six genes are expressed throughout muscle development, in embryonic and adult proliferating myogenic stem cells and in fetal and adult post-mitotic myofibers, where SIX proteins regulate the expression of various categories of genes. In vivo, SIX proteins control many steps of muscle development, acting through feedforward mechanisms: in the embryo for myogenic fate acquisition through the direct control of Myogenic Regulatory Factors; in adult myofibers for their contraction/relaxation and fatigability properties through the control of genes involved in metabolism, sarcomeric organization and calcium homeostasis. Furthermore, during development and in the adult, SIX homeoproteins participate in the genesis and the maintenance of myofibers diversity.
最初在果蝇中描述了六种 homeoprotein，它们与 eyeless、eyes absent 和 dachsund 一起参与 Pax-Six-Eya-Dach (PSED) 网络，通过遗传和生化相互作用协同驱动眼睛发育。随后在脊椎动物中确定了 PSED 网络和 SIX 蛋白在肌肉形成中的作用。EYA 和 DACH 蛋白与 SIX 转录复合物 (STC) 的保守相互作用是胚胎发生和成年肌纤维中 STC 活性的基础。Six 基因在整个肌肉发育过程中表达，在胚胎和成年增殖性肌源性干细胞以及胎儿和成年有丝分裂后肌纤维中表达，其中 SIX 蛋白调节各种类别的基因的表达。在体内，SIX 蛋白通过前馈机制控制许多肌肉发育步骤，在胚胎中通过直接控制肌生成调节因子来获得肌生成命运；在成年肌纤维中，通过控制参与代谢、肌节组织和钙稳态的基因来控制其收缩/松弛和疲劳特性。此外，在发育和成年过程中，SIX homeoprotein 参与肌纤维多样性的产生和维持。
