Centre for Haematology, Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
School of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
Biomolecules. 2021 Jun 7;11(6):849. doi: 10.3390/biom11060849.
Notch signaling forms an evolutionarily conserved juxtacrine pathway crucial for cellular development. Initially identified in wing morphogenesis, Notch signaling has since been demonstrated to play pivotal roles in governing mammalian cellular development in a large variety of cell types. Indeed, abolishing Notch constituents in mouse models result in embryonic lethality, demonstrating that Notch signaling is critical for development and differentiation. In this review, we focus on the crucial role of Notch signaling in governing embryogenesis and differentiation of multiple progenitor cell types. Using hematopoiesis as a diverse cellular model, we highlight the role of Notch in regulating the cell fate of common lymphoid progenitors. Additionally, the influence of Notch through microenvironment interplay with lymphoid cells and how dysregulation influences disease processes is explored. Furthermore, bi-directional and lateral Notch signaling between ligand expressing source cells and target cells are investigated, indicating potentially novel therapeutic options for treatment of Notch-mediated diseases. Finally, we discuss the role of cis-inhibition in regulating Notch signaling in mammalian development.
Notch 信号通路形成了一种进化上保守的旁分泌途径，对细胞发育至关重要。Notch 信号通路最初在 wing 形态发生中被识别，此后已被证明在调控哺乳动物多种细胞类型的细胞发育中发挥关键作用。事实上，在小鼠模型中敲除 Notch 成分会导致胚胎致死，这表明 Notch 信号通路对发育和分化至关重要。在这篇综述中，我们重点介绍 Notch 信号通路在调控多种祖细胞类型的胚胎发生和分化中的关键作用。我们使用造血作为一个多样化的细胞模型，强调 Notch 在调节共同淋巴祖细胞的细胞命运中的作用。此外，还探讨了 Notch 通过与淋巴样细胞的微环境相互作用以及失调如何影响疾病过程的影响。此外，还研究了配体表达源细胞和靶细胞之间的双向和侧向 Notch 信号，表明可能存在治疗 Notch 介导疾病的新的治疗选择。最后，我们讨论了 cis 抑制在调节哺乳动物发育中 Notch 信号通路的作用。
