Computer simulation of emerging asymmetry in the mouse blastocyst
Computer simulation of emerging asymmetry in the mouse blastocyst
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DOI：
10.1242/dev.014555
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发表时间：
2008-04-15
期刊：
影响因子：
4.6
通讯作者：
Hiiragi, Takashi
中科院分区：
文献类型：
--
作者：
Honda, Hisao;Motosugi, Nami;Hiiragi, Takashi
哺乳动物胚胎极性建立的机制一直存在争议。尽管有些人声称在卵中存在预图案，但我们最近提出的证据表明小鼠胚胎极性直到囊胚才建立，并提出了机械约束模型。在这里，我们应用计算机模拟来澄清这种形态所需的最小细胞特性。该模拟基于三个假设：（1）细胞聚集体的行为由3D顶点动力学模型模拟;（2）所有细胞具有等效的力学性质;（3）具有等效表面性质的内腔逐渐扩大。然而，最初的尝试揭示了一个额外的假设的要求：（4）腔的表面比细胞间表面更坚固，这表明存在基底膜内衬胚泡腔，这确实是由已发表的数据证实。因此，该模拟成功地产生了重现小鼠胚泡的结构。然而，囊胚的轴仍然是可变的，这使我们有了一个额外的假设：（5）聚集体被一个囊包封，相当于体内的透明囊。球形囊不能稳定胚泡轴，而椭圆形囊最终根据其最长直径确定轴的方向。这些预测通过对小鼠胚胎的延时记录得到了实验验证。在模拟过程中，等效细胞形成由较小的内部细胞和较大的外部细胞组成的两个不同的群体。这些结果揭示了一个独特的功能，早期哺乳动物的发展：不对称性可能会出现自主在一个等效的人口，不需要先验的内在差异。
The mechanism of embryonic polarity establishment in mammals has long been controversial. Whereas some claim prepatterning in the egg, we recently presented evidence that mouse embryonic polarity is not established until blastocyst and proposed the mechanical constraint model. Here we apply computer simulation to clarify the minimal cellular properties required for this morphology. The simulation is based on three assumptions: (1) behavior of cell aggregates is simulated by a 3D vertex dynamics model; (2) all cells have equivalent mechanical properties; (3) an inner cavity with equivalent surface properties is gradually enlarged. However, an initial attempt reveals a requirement for an additional assumption: (4) the surface of the cavity is firmer than intercellular surfaces, suggesting the presence of a basement membrane lining the blastocyst cavity, which is indeed confirmed by published data. The simulation thus successfully produces a structure recapitulating the mouse blastocyst. The axis of the blastocyst, however, remains variable, leading us to an additional assumption: (5) the aggregate is enclosed by a capsule, equivalent to the zona pellucida in vivo. Whereas a spherical capsule does not stabilize the blastocyst axis, an ellipsoidal capsule eventually orients the axis in accordance with its longest diameter. These predictions are experimentally verified by time-lapse recordings of mouse embryos. During simulation, equivalent cells form two distinct populations composed of smaller inner cells and larger outer cells. These results reveal a unique feature of early mammalian development: an asymmetry may emerge autonomously in an equivalent population with no need for a priori intrinsic differences.