Centre for Advanced Computational Science, Manchester Metropolitan University, Manchester M15 6BH, UK.
BioEmergences, FRE2039, CNRS Université Paris Saclay, Gif-sur-Yvette 91190, France.
Bioinformatics. 2021 Sep 29;37(18):2946-2954. doi: 10.1093/bioinformatics/btab201.
Understanding the mechanisms by which the zebrafish pectoral fin develops is expected to produce insights on how vertebrate limbs grow from a 2D cell layer to a 3D structure. Two mechanisms have been proposed to drive limb morphogenesis in tetrapods: a growth-based morphogenesis with a higher proliferation rate at the distal tip of the limb bud than at the proximal side, and directed cell behaviors that include elongation, division and migration in a non-random manner. Based on quantitative experimental biological data at the level of individual cells in the whole developing organ, we test the conditions for the dynamics of pectoral fin early morphogenesis.
We found that during the development of the zebrafish pectoral fin, cells have a preferential elongation axis that gradually aligns along the proximodistal (PD) axis of the organ. Based on these quantitative observations, we build a center-based cell model enhanced with a polarity term and cell proliferation to simulate fin growth. Our simulations resulted in 3D fins similar in shape to the observed ones, suggesting that the existence of a preferential axis of cell polarization is essential to drive fin morphogenesis in zebrafish, as observed in the development of limbs in the mouse, but distal tip-based expansion is not.
Upon publication, biological data will be available at http://bioemergences.eu/modelingFin, and source code at https://github.com/guijoe/MaSoFin.
Supplementary data are available at Bioinformatics online.
了解斑马鱼胸鳍发育的机制有望深入了解脊椎动物四肢如何从二维细胞层生长成三维结构。有两种机制被提出来驱动四足动物的肢体形态发生：一种是基于生长的形态发生，肢芽远端的增殖率高于近端；另一种是定向的细胞行为，包括以非随机的方式伸长、分裂和迁移。基于个体细胞在整个发育器官水平上的定量实验生物学数据，我们检验了胸鳍早期形态发生动力学的条件。
我们发现，在斑马鱼胸鳍的发育过程中，细胞具有优先伸长轴，该轴逐渐沿着器官的近-远轴（PD）对齐。基于这些定量观察，我们构建了一个以中心为基础的细胞模型，增强了极性项和细胞增殖，以模拟鳍的生长。我们的模拟结果得到了与观察到的形状相似的 3D 鳍，表明细胞极化的优先轴的存在对于驱动斑马鱼鳍的形态发生是至关重要的，就像在小鼠四肢发育中观察到的那样，但基于远端尖端的扩张并不是必需的。
出版后，生物数据将可在 http://bioemergences.eu/modelingFin 获得，源代码将可在 https://github.com/guijoe/MaSoFin 获得。
补充数据可在生物信息学在线获得。
