The Francis Crick Institute, London, United Kingdom.
The Francis Crick Institute, London, United Kingdom.
Curr Top Dev Biol. 2020;139:239-266. doi: 10.1016/bs.ctdb.2020.03.003. Epub 2020 May 4.
Tightly regulated gene expression programs, orchestrated by complex interactions between transcription factors, control cell type specification during development. Repressive interactions play a critical role in these networks, facilitating decision-making between two or more alternative cell fates. Here, we use the ventral neural tube as an example to illustrate how cross repressive interactions within a network drive pattern formation and specify cell types in response to a graded patterning signal. This and other systems serve to highlight how external signals are integrated through the cis regulatory elements controlling key genes and provide insight into the molecular underpinning of the process. Even the simplest networks can lead to counterintuitive results and we argue that a combination of experimental dissection and modeling approaches will be necessary to fully understand network behavior and the underlying design principles. Studying these gene regulatory networks as a whole ultimately allows us to extract fundamental properties applicable across systems that can expand our mechanistic understanding of how organisms develop.
严格调控的基因表达程序，由转录因子之间的复杂相互作用协调，控制着发育过程中的细胞类型特化。抑制性相互作用在这些网络中起着关键作用，促进了两个或多个替代细胞命运之间的决策。在这里，我们以腹侧神经管为例来说明网络内的交叉抑制性相互作用如何驱动模式形成，并响应分级模式信号来指定细胞类型。这个系统和其他系统突出了外部信号如何通过控制关键基因的顺式调控元件进行整合，并提供了对该过程分子基础的深入了解。即使是最简单的网络也可能导致违反直觉的结果，我们认为，实验剖析和建模方法的结合将是充分理解网络行为和潜在设计原则所必需的。作为一个整体来研究这些基因调控网络，最终使我们能够提取出适用于整个系统的基本属性，从而扩展我们对生物体如何发育的机械理解。
