Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:4143-4146. doi: 10.1109/EMBC46164.2021.9629491.
Notch signaling (NS) determines the fate of adjacent cells during metazoans development. This intercellular signaling mechanism regulates diverse development processes like cell differentiation, proliferation, survival and is considered responsible for maintaining cellular homeostasis. In this study, we elucidate the role of Notch heterogeneity (NH) in cell fate determination. We studied the role of NH at intercellular, intracellular and the coexistence of Notch variation simultaneously at the intracellular and intercellular level in direct cell-cell signaling on an irregular cell mosaic. In addition, the effect of intracellular Notch receptor diffusion on an irregular cell lattice is also taken into account during Delta-Notch lateral inhibition (LI) process. Through mathematical and computational models, we discovered that the classical checkerboard pattern formation can be reproduced with an accuracy of 70-81% by accounting for NH in a realistic epithelial layer of multicellular organisms.
Notch 信号（NS）在后生动物发育过程中决定相邻细胞的命运。这种细胞间信号机制调节多种发育过程，如细胞分化、增殖、存活，被认为负责维持细胞内稳态。在这项研究中，我们阐明了 Notch 异质性（NH）在细胞命运决定中的作用。我们研究了 NH 在细胞间、细胞内以及 Notch 变异同时共存的作用，即在不规则细胞嵌合体上的直接细胞-细胞信号传递中。此外，在 Delta-Notch 侧向抑制（LI）过程中，还考虑了细胞内 Notch 受体扩散对不规则细胞晶格的影响。通过数学和计算模型，我们发现通过在多细胞生物的真实上皮层中考虑 NH，可以以 70-81%的精度重现经典的棋盘图案形成。
