Robust mechanisms of ventral furrow invagination require the combination of cellular shape changes

Robust mechanisms of ventral furrow invagination require the combination of cellular shape changes
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DOI:
10.1088/1478-3975/6/1/016010
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发表时间:
2009-03-01
期刊:
影响因子:
2
通讯作者:
Miodownik, Mark
Miodownik, Mark
中科院分区:
生物学4区
文献类型:
--
作者:
Conte, Vito;Munoz, Jose J.;Miodownik, Mark

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果蝇腹侧沟的形成是胚胎生命中第一次大规模的形态发生运动,由细胞胚层内单个上皮细胞形状的协调变化驱动。虽然许多涉及的基因已经被识别,但将基因表达的局部变化转化为胚胎形式的整体变化的机械过程的细节仍有待完全了解。生物学家已经确定了导致腹侧沟内陷的两种主要细胞变形模式:细胞顶端的收缩(尖端楔形)和沿其顶端-基底轴的变形(径向延长/缩短)。在这项工作中,我们使用腹侧沟形成的计算机2D有限元模型来研究三种可能的基本活动细胞形状变化的不同组合导致上皮内陷的能力:外胚层顶端-基底部缩短、中胚层顶端-基端延长/缩短和中胚层顶端收缩。我们对生物力学系统进行了系统的分析,发现许多不同的主动力量组合(内陷机制)能够产生腹侧皱纹。揭示了两个重要的一般特征。首先,形状变化的组合对环境和突变扰动是最健壮的,特别是那些结合了外胚层推动和中胚层楔入的组合。其次,外胚层推动在所有强健的机制中发挥了重要作用(仅靠中胚层力量并不能关闭皱纹),这提供了证据,表明它可能是果蝇内陷机制中的一个重要因素。
Ventral furrow formation in Drosophila is the first large-scale morphogenetic movement during the life of the embryo, and is driven by co-ordinated changes in the shape of individual epithelial cells within the cellular blastoderm. Although many of the genes involved have been identified, the details of the mechanical processes that convert local changes in gene expression into whole-scale changes in embryonic form remain to be fully understood. Biologists have identified two main cell deformation modes responsible for ventral furrow invagination: constriction of the apical ends of the cells (apical wedging) and deformation along their apical-basal axes (radial lengthening/shortening). In this work, we used a computer 2D finite element model of ventral furrow formation to investigate the ability of different combinations of three plausible elementary active cell shape changes to bring about epithelial invagination: ectodermal apical-basal shortening, mesodermal apical-basal lengthening/shortening and mesodermal apical constriction. We undertook a systems analysis of the biomechanical system, which revealed many different combinations of active forces (invagination mechanisms) were able to generate a ventral furrow. Two important general features were revealed. First that combinations of shape changes are the most robust to environmental and mutational perturbation, in particular those combining ectodermal pushing and mesodermal wedging. Second, that ectodermal pushing plays a big part in all of the robust mechanisms (mesodermal forces alone do not close the furrow), and this provides evidence that it may be an important element in the mechanics of invagination in Drosophila.