Scaling of embryonic patterning based on phase-gradient encoding

摘要

A fundamental feature of embryonic patterning is the ability to scale and maintain stable proportions despite changes in overall size, for instance during growth. A notable example occurs during vertebrate segment formation: after experimental reduction of embryo size, segments form proportionally smaller, and consequently, a normal number of segments is formed. Despite decades of experimental and theoretical work, the underlying mechanism remains unknown. More recently, ultradian oscillations in gene activity have been linked to the temporal control of segmentation; however, their implication in scaling remains elusive. Here we show that scaling of gene oscillation dynamics underlies segment scaling. To this end, we develop a new experimental model, an ex vivo primary cell culture assay that recapitulates mouse mesoderm patterning and segment scaling, in a quasi-monolayer of presomitic mesoderm cells (hereafter termed monolayer PSM or mPSM). Combined with real-time imaging of gene activity, this enabled us to quantify the gradual shift in the oscillation phase and thus determine the resulting phase gradient across the mPSM. Crucially, we show that this phase gradient scales by maintaining a fixed amplitude across mPSM of different lengths. We identify the slope of this phase gradient as a single predictive parameter for segment size, which functions in a size- and temperature-independent manner, revealing a hitherto unrecognized mechanism for scaling. Notably, in contrast to molecular gradients, a phase gradient describes the distribution of a dynamical cellular state. Thus, our phase-gradient scaling findings reveal a new level of dynamic information-processing, and provide evidence for the concept of phase-gradient encoding during embryonic patterning and scaling.%一种发育中的生物怎样在生长过程中维持其身rn体比例?这个过程被称为比例缩放(scaling)，rn但我们对它却知之甚少。这篇论文介绍了研究rn生物学中这一基本问题的一个新模型：在培养rn皿中的一个活体外的中胚层细胞培养，中胚层rn模式形成及体节形成连同比例缩放都在该培养rn皿中发生。利用这种方法，本文作者发现，胚rn胎利用周期性(振荡性)基因活性来维持其比rn例。这种周期性基因活性对胚胎总体大小做出rn反应，反过来又控制胚胎结构的形成。