Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan.
Elife. 2020 May 29;9:e53608. doi: 10.7554/eLife.53608.
The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of genes are not fully understood. In this study, we demonstrated that the / pathway is critical for axial elongation. mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of in mice resulted in the reduction of PRC1 occupancy at the cluster loci by targeting . Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior genes, which was rescued by the knockdown of . These results suggest that the / pathway is involved in the modulation of the ' code' via regulation during axial patterning.
基因在时空表达上决定了沿体轴的体节模式和区域特征。其独特表达模式需要多步调控；然而，对于基因的严格调控背后的分子机制还不完全清楚。在这项研究中，我们证明了 / 通路对于轴的伸长是至关重要的。/ 缺失的小鼠表现出轴向缩短，伴有轻微的椎骨骨骼转化，这与尾巴芽特异性 Lin28a 突变体的小鼠结果一致。/ 缺失的小鼠中 积累，导致 PRC1 占据物在 簇基因座的减少，通过靶向 来实现。一致地，胚胎干细胞样细胞中 Lin28a 的缺失导致后部 基因的异常诱导，而 的敲低可以挽救这一现象。这些结果表明，/ 通路通过在轴向模式形成过程中调节 来参与“代码”的调制。
