Muscle Biology Laboratory, Research Team for Aging Science, Tokyo Metropolitan Institute for Geriatrics and Gerontology (TMIG), 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
Department of Muscle Development and Regeneration, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan.
J Biochem. 2024 Sep 30;176(4):277-283. doi: 10.1093/jb/mvae059.
The skeletal muscle is a contractile tissue distributed throughout the body with various anatomical sizes, shapes and functions. In pathological conditions, such as muscular dystrophy, age-related sarcopenia and cancer cachexia, skeletal muscles are not uniformly affected throughout the body. This region-specific vulnerability cannot be fully explained by known physiological classifications, including muscle fiber types. Accumulating evidence indicates that the expression patterns of topographic homeobox (Hox) genes provide a molecular signature of positional memory, reflecting the anatomical locations and embryonic history of muscles and their associated muscle stem cells in adult mice and humans. Hox-based positional memory is not merely a remnant of embryonic development but is expected to be an intrinsic determinant controlling muscle function because recent studies have shown that aberrant Hox genes affect muscle stem cells. In this review, we discuss the concept of Hox-based positional memory, which may offer a new perspective on the region-specific pathophysiology of muscle disorders.
骨骼肌是一种分布于全身的可收缩组织，具有各种解剖学大小、形状和功能。在病理条件下，如肌肉营养不良、与年龄相关的肌肉减少症和癌症恶病质，全身的骨骼肌并非均匀受影响。这种区域特异性易损性不能用已知的生理分类（包括肌纤维类型）完全解释。越来越多的证据表明，拓扑同源盒（Hox）基因的表达模式提供了位置记忆的分子特征，反映了成年小鼠和人类肌肉及其相关肌肉干细胞的解剖位置和胚胎史。基于 Hox 的位置记忆不仅仅是胚胎发育的残余，而是有望成为控制肌肉功能的内在决定因素，因为最近的研究表明，异常的 Hox 基因会影响肌肉干细胞。在这篇综述中，我们讨论了基于 Hox 的位置记忆的概念，这可能为肌肉疾病的区域特异性病理生理学提供新的视角。
