A cell-size threshold limits cell polarity and asymmetric division potential

First author: Lars Hubatsch; Affiliations: The Francis Crick Institute (弗朗西斯·克里克研究所): London, UK

Corresponding author: Nathan W. Goehring

Reaction–diffusion networks underlie pattern formation in a range of biological contexts, from morphogenesis of organisms to the polarization of individual cells. One requirement for such molecular networks is that output patterns be scaled to system size. At the same time, kinetic properties of constituent molecules constrain the ability of networks to adapt to size changes. Here, we explore these constraints and the consequences thereof within the conserved PAR cell polarity network. Using the stem-cell-like germ lineage of the Caenorhabditis elegans embryo as a model, we find that the behaviour of PAR proteins fails to scale with cell size. Theoretical analysis demonstrates that this lack of scaling results in a size threshold below which polarity is destabilized, yielding an unpolarized system. In empirically constrained models, this threshold occurs near the size at which germ lineage cells normally switch between asymmetric and symmetric modes of division. Consistent with cell size limiting polarity and division asymmetry, genetic or physical reduction in germ lineage cell size is sufficient to trigger loss of polarity in normally polarizing cells at predicted size thresholds. Physical limits of polarity networks may be one mechanism by which cells read out geometrical features to inform cell fate decisions.

反应-扩散网络从各个方面构成了模式建成的基础，大到器官的形态建成，小到单个细胞的极性。这种分子网络的其中一个条件就是输出的模式可以扩展到系统大小。同时，组成该网络的分子组份的动力学特性又限制了网络适应大小变化的能力。本文中，作者研究了保守的PAR细胞极性系统中的限制条件以及带来的后果。利用秀丽隐杆线虫胚胎的类似于干细胞的生殖系作为研究模型，作者发现PAR蛋白的行为并不能扩展到细胞大小。理论分析显示这种扩展能力的缺失会导致细胞极性的稳定需要一个细胞大小的阈值，若是低于这个阈值则会产生一个非极性的系统。在经验限制模型中，该阈值应该比较接近生殖系细胞在对称和非对称分裂可以正常转换时的细胞大小。与细胞大小限制极性和不对称分裂一致的是，遗传和物理手段减小生殖系细胞的大小足以诱导正常状态下具有极性的细胞在预期阈值大小时丢失极性。极性网络的物理限制可能是细胞通过几何特征决定细胞命运决定的机制之一。

通讯：Nathan W. Goehring  (https://goehringlab.crick.ac.uk/the-team/nate-goehring.html)

个人简介：1994-1998年，阿姆赫斯特学院，学士；1999-2006年，哈佛医学院，博士；2006-2012年，马克斯普朗克分子细胞生物学和遗传学研究所，博士后。  

研究方向：细胞极性。

doi: https://doi.org/10.1038/s41567-019-0601-x

Journal: Nature Physics

Published date: August 12, 2019