Bryant Susan V, Gardiner David M
Department of Developmental and Cell Biology.
University of California Irvine Irvine California.
Regeneration (Oxf). 2016 Apr 28;3(2):103-22. doi: 10.1002/reg2.55. eCollection 2016 Apr.
Successful development depends on the creation of spatial gradients of transcription factors within developing fields, and images of graded distributions of gene products populate the pages of developmental biology journals. Therefore the challenge is to understand how the graded levels of intracellular transcription factors are generated across fields of cells. We propose that transcription factor gradients are generated as a result of an underlying gradient of cell cycle lengths. Very long cell cycles will permit accumulation of a high level of a gene product encoded by a large transcription unit, whereas shorter cell cycles will permit progressively fewer transcripts to be completed due to gating of transcription by the cell cycle. We also propose that the gradients of cell cycle lengths are generated by gradients of extracellular morphogens/growth factors. The model of cell cycle gated transcriptional regulation brings focus back to the functional role of morphogens as cell cycle regulators, and proposes a specific and testable mechanism by which morphogens, in their roles as growth factors (how they were originally discovered), also determine cell fate.
成功的发育依赖于在发育区域内形成转录因子的空间梯度,基因产物梯度分布的图像充斥着发育生物学杂志的页面。因此,挑战在于理解细胞内转录因子的梯度水平是如何在细胞区域中产生的。我们提出,转录因子梯度是细胞周期长度潜在梯度的结果。非常长的细胞周期将允许由大转录单位编码的高水平基因产物积累,而较短的细胞周期由于细胞周期对转录的门控作用,将允许完成的转录本逐渐减少。我们还提出,细胞周期长度的梯度是由细胞外形态发生素/生长因子的梯度产生的。细胞周期门控转录调控模型将焦点重新带回形态发生素作为细胞周期调节剂的功能作用,并提出了一种特定且可测试的机制,通过该机制,形态发生素在其作为生长因子的角色中(它们最初就是这样被发现的),也决定了细胞命运。