无需形态素梯度的基因表达稳定发育模式
Stable developmental patterns of gene expression without morphogen gradients
AI总结：
本研究结合空间随机模拟与稳定性理论，揭示了在无形态素梯度时，通过微调基因间弱抑制相互作用至最优水平，可产生亚稳态吸引子，从而将基因表达模式的时间稳定性提升数个数量级。
摘要：
基因表达模式（GEPs）是由解读形态素梯度的交叉调控靶基因建立的。然而，随着发育的推进，形态素活性降低，使得新出现的GEP失去了稳定的位置线索。随后，GEP可能会被在细胞水平上起作用的内在噪声生化过程所破坏。然而，在许多生物系统中，已建立的GEP在时空上保持稳定。在此，我们结合空间随机模拟、增强采样方法（非平稳前向通量采样）以及最近开发的稳定性理论，以解决在没有形态素梯度的情况下如何维持GEP时空完整性的问题。使用由空间耦合生化反应器体积组成的最小胚胎模型，我们研究了条纹模式，其中最近邻域之间的弱交叉抑制与次近邻域之间的强抑制交替出现，该研究受Drosophila胚胎中gap基因系统启发。我们发现，将弱抑制相互作用微调至最佳水平，可将GEP的时间稳定性提高数个数量级，从而在没有形态素梯度的情况下提供发育相关时间内的稳定性。通过数值确定的最佳参数范围与稳定性理论的预测高度一致。通过分析GEP不对称因子的动力学，我们将模式稳定性的增强追溯到亚稳态盆地的出现以及抵消模式扰动的恢复力。这些力的起源通过有效模型得到了进一步解释，该模型描述了系统新出现的确定性动力学。总而言之，我们表明，只要塑造模式的基因调控相互作用得到最佳微调，即使没有系统范围的位置线索，亚稳态吸引子也可以作为随机GEP的属性出现。
英文摘要：
Gene expression patterns (GEPs) are established by cross-regulating target genes that interpret morphogen gradients. However, as development progresses, morphogen activity is reduced, leaving the emergent GEP without stabilizing positional cues. The GEP then can be deteriorated by the intrinsically noisy biochemical processes acting at the cellular level. However, the established GEPs remain spatio-temporally stable in many biological systems. Here we combine spatial-stochastic simulations with an enhanced sampling method (Non-Stationary Forward Flux Sampling) and a recently developed stability theory to address how spatiotemporal integrity of a GEP is maintained without morphogen gradients. Using a minimal embryo model consisting of spatially coupled biochemical reactor volumes, we study a stripe pattern in which weak cross-repression between nearest neighbor domians alternates with strong repression between next-nearest neighbor domains, inspired by the gap gene system in the Drosophila embryo. We find that fine-tuning of the weak repressive interactions to an optimal level increases temporal stability of GEPs by orders of magnitude, providing stability over developmentally relevant times, without morphogen gradients. The numerically determined optimal parameter regime closely agrees with the predictions of the stability theory. By analizing the dynamics of GEP asymmetry factors, we trace back the pattern stability enhancement to the emergence of a metastable basin and restoring forces that counteract pattern perturbations. The origin of these forces is further explained by the effective model, describing the emergent deterministic dynamics of the system. Altogether, we show that metastable attractors can emerge as a property of stochastic GEPs even without system-wide positional cues, provided that the gene regulatory interactions shaping the pattern are optimally tuned.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
