Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Dev Cell. 2019 Oct 7;51(1):49-61.e4. doi: 10.1016/j.devcel.2019.08.005. Epub 2019 Sep 5.
As epithelial tissues develop, groups of cells related by descent tend to associate in clonal populations rather than dispersing within the cell layer. While this is frequently assumed to be a result of differential adhesion, precise mechanisms controlling clonal cohesiveness remain unknown. Here we employ computational simulations to modulate epithelial cell size in silico and show that junctions between small cells frequently collapse, resulting in clone-cell dispersal among larger neighbors. Consistent with similar dynamics in vivo, we further demonstrate that mosaic disruption of Drosophila Tor generates small cells and results in aberrant clone dispersal in developing wing disc epithelia. We propose a geometric basis for this phenomenon, supported in part by the observation that soap-foam cells exhibit similar size-dependent junctional rearrangements. Combined, these results establish a link between cell-size pleomorphism and the control of epithelial cell packing, with potential implications for understanding tumor cell dispersal in human disease.
当上皮组织发育时，具有亲缘关系的细胞群体往往倾向于聚集在克隆群体中，而不是在细胞层内分散。虽然这通常被认为是细胞间黏附的差异造成的，但控制克隆黏附的精确机制仍不清楚。在这里，我们通过计算模拟来调节上皮细胞的大小，并表明小细胞之间的连接经常会崩溃，导致克隆细胞在较大的相邻细胞中分散。与体内类似的动态一致，我们进一步证明，果蝇 Tor 的镶嵌破坏会产生小细胞，并导致发育中的翅膀盘上皮细胞中异常的克隆细胞分散。我们提出了一个解释这一现象的几何基础，部分原因是观察到肥皂泡细胞表现出类似的与细胞大小相关的连接重排。综合这些结果，建立了细胞大小多态性与上皮细胞排列控制之间的联系，这可能对理解人类疾病中肿瘤细胞的扩散有一定的启示。
