Li Yingzi, Naveed Hammad, Kachalo Sema, Xu Lisa X, Liang Jie
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China ; Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States of America ; CAS-MPG Partner Institute for Computational Biology, SIBS, CAS, Shanghai, China.
PLoS One. 2014 Feb 4;9(2):e86725. doi: 10.1371/journal.pone.0086725. eCollection 2014.
Regulation of cell growth and cell division plays fundamental roles in tissue morphogenesis. However, the mechanisms of regulating tissue elongation through cell growth and cell division are still not well understood. The wing imaginal disc of Drosophila provides a model system that has been widely used to study tissue morphogenesis. Here we use a recently developed two-dimensional cellular model to study the mechanisms of regulating tissue elongation in Drosophila wing. We simulate the effects of directional cues on tissue elongation. We also computationally analyze the role of reduced cell size. Our simulation results indicate that oriented cell divisions, oriented mechanical forces, and reduced cell size can all mediate tissue elongation, but they function differently. We show that oriented cell divisions and oriented mechanical forces act as directional cues during tissue elongation. Between these two directional cues, oriented mechanical forces have a stronger influence than oriented cell divisions. In addition, we raise the novel hypothesis that reduced cell size may significantly promote tissue elongation. We find that reduced cell size alone cannot drive tissue elongation. However, when combined with directional cues, such as oriented cell divisions or oriented mechanical forces, reduced cell size can significantly enhance tissue elongation in Drosophila wing. Furthermore, our simulation results suggest that reduced cell size has a short-term effect on cell topology by decreasing the frequency of hexagonal cells, which is consistent with experimental observations. Our simulation results suggest that cell divisions without cell growth play essential roles in tissue elongation.
细胞生长和细胞分裂的调控在组织形态发生中起着基础性作用。然而,通过细胞生长和细胞分裂来调控组织伸长的机制仍未被充分理解。果蝇的翅成虫盘提供了一个被广泛用于研究组织形态发生的模型系统。在此,我们使用最近开发的二维细胞模型来研究果蝇翅中组织伸长的调控机制。我们模拟了定向线索对组织伸长的影响。我们还通过计算分析了细胞尺寸减小的作用。我们的模拟结果表明,定向细胞分裂、定向机械力和细胞尺寸减小都能介导组织伸长,但它们的作用方式不同。我们表明,定向细胞分裂和定向机械力在组织伸长过程中充当定向线索。在这两种定向线索之间,定向机械力比定向细胞分裂的影响更强。此外,我们提出了一个新的假说,即细胞尺寸减小可能会显著促进组织伸长。我们发现仅细胞尺寸减小并不能驱动组织伸长。然而,当与定向线索,如定向细胞分裂或定向机械力相结合时,细胞尺寸减小能显著增强果蝇翅中的组织伸长。此外,我们的模拟结果表明,细胞尺寸减小通过降低六边形细胞的频率对细胞拓扑结构有短期影响,这与实验观察结果一致。我们的模拟结果表明,没有细胞生长的细胞分裂在组织伸长中起着至关重要的作用。