看看是谁在发挥mTOR作用:mTOR在肢体发育和软骨内骨生长过程中介导细胞状态与外部信号的整合。

Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.

作者信息

H'ng Chee Ho, Khaladkar Ashwini, Rosello-Diez Alberto

机构信息

Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.

Department of Biochemistry, Central University of Hyderabad, Hyderabad, India.

出版信息

Front Cell Dev Biol. 2023 Apr 19;11:1153473. doi: 10.3389/fcell.2023.1153473. eCollection 2023.

Abstract

The balance of cell proliferation and size is key for the control of organ development and repair. Moreover, this balance has to be coordinated within tissues and between tissues to achieve robustness in the organ's pattern and size. The tetrapod limb has been used to study these topics during development and repair, and several conserved pathways have emerged. Among them, mechanistic target of rapamycin (mTOR) signaling, despite being active in several cell types and developmental stages, is one of the least understood in limb development, perhaps because of its multiple potential roles and interactions with other pathways. In the body of this review, we have collated and integrated what is known about the role of mTOR signaling in three aspects of tetrapod limb development: 1) limb outgrowth; 2) chondrocyte differentiation after mesenchymal condensation and 3) endochondral ossification-driven longitudinal bone growth. We conclude that, given its ability to interact with the most common signaling pathways, its presence in multiple cell types, and its ability to influence cell proliferation, size and differentiation, the mTOR pathway is a critical integrator of external stimuli and internal status, coordinating developmental transitions as complex as those taking place during limb development. This suggests that the study of the signaling pathways and transcription factors involved in limb patterning, morphogenesis and growth could benefit from probing the interaction of these pathways with mTOR components.

摘要

细胞增殖与大小的平衡是控制器官发育和修复的关键。此外,这种平衡必须在组织内部以及组织之间进行协调,以实现器官形态和大小的稳健性。四足动物的肢体已被用于研究发育和修复过程中的这些主题,并且已经出现了几种保守的信号通路。其中,雷帕霉素的机制性靶点(mTOR)信号通路,尽管在多种细胞类型和发育阶段都有活性,但在肢体发育中却是了解最少的之一,这可能是因为它具有多种潜在作用以及与其他信号通路的相互作用。在本综述中,我们整理并整合了关于mTOR信号通路在四足动物肢体发育的三个方面所起作用的已知信息:1)肢体生长;2)间充质凝聚后软骨细胞的分化;3)软骨内成骨驱动的纵向骨生长。我们得出结论,鉴于mTOR信号通路能够与最常见的信号通路相互作用、存在于多种细胞类型中以及能够影响细胞增殖、大小和分化,mTOR信号通路是外部刺激和内部状态的关键整合者,协调着肢体发育过程中发生的复杂发育转变。这表明,对参与肢体模式形成、形态发生和生长的信号通路和转录因子的研究可能会受益于探究这些信号通路与mTOR组分之间的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d49e/10154674/87325215fe99/fcell-11-1153473-g001.jpg

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