Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Molecular and Developmental Biology Graduate Program, University of Cincinnati, College of Medicine, Cincinnati, OH, 45229, USA.
Nat Commun. 2023 Oct 14;14(1):6497. doi: 10.1038/s41467-023-42220-7.
Mutations of several genes cause incomplete penetrance and variable expressivity of phenotypes, which are usually attributed to modifier genes or gene-environment interactions. Here, we show stochastic gene expression underlies the variability of somite segmentation defects in embryos mutant for segmentation clock genes her1 or her7. Phenotypic strength is further augmented by low temperature and hypoxia. By performing live imaging of the segmentation clock reporters, we further show that groups of cells with higher oscillation amplitudes successfully form somites while those with lower amplitudes fail to do so. In unfavorable environments, the number of cycles with high amplitude oscillations and the number of successful segmentations proportionally decrease. These results suggest that individual oscillation cycles stochastically fail to pass a threshold amplitude, resulting in segmentation defects in mutants. Our quantitative methodology is adaptable to investigate variable phenotypes of mutant genes in different tissues.
基因突变会导致表型不完全外显和表现度变异，这通常归因于修饰基因或基因-环境相互作用。在这里，我们表明，随机基因表达是导致 Her1 或 Her7 分割时钟基因突变胚胎体节分割缺陷变异性的基础。表型强度进一步通过低温和缺氧增强。通过对分割时钟报告基因进行活细胞成像，我们进一步表明，具有较高振荡幅度的细胞群成功形成体节，而具有较低幅度的细胞群则无法形成体节。在不利环境下，具有高振幅振荡的循环次数和成功分割的次数成比例减少。这些结果表明，单个振荡循环随机未能通过阈值幅度，导致突变体的分割缺陷。我们的定量方法适用于研究不同组织中突变基因的可变表型。
