Repressive interactions in gene regulatory networks: When you have no other choice

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.