The Toggle Switch Model for Gene Expression Change during the Prenatal-to-Postnatal Transition in Mammals

The prenatal-to-postnatal transition is a pivotal process in the life cycle whereby an organism shifts from responding to intrauterine cues to undergoing extrauterine stresses with many physiological adaptations. However, the molecular basis underlying the evolutionarily conserved physiological adaptations remains elusive. Here, we analyze the transcriptomes of seven organs across developmental time points from five mammalian species by constructing computational coexpression networks and report a developmental shift of gene expression at the perinatal stage. The low-to-high and high-to-low expressed genes tightly coalesce in the functional categories and gene regulatory pathways that implicate the physiological adaptions during the prenatal-to-postnatal transition, including lipid metabolism, circadian rhythm, immune response, cell cycle, and cell division. The low-to-high and high-to-low expressed genes around the perinatal stage tend to form the mutually inhibitory toggle switch gene pairs linking the gene regulatory networks in response to the environmental changes. We thus propose the toggle switch model for the developmental shift of gene expression as a mechanic framework to investigate how the physiological adaptations occur during the prenatal-to-postnatal transition.

Automated summary

The prenatal-to-postnatal transition is a crucial process in an organism's life cycle, involving physiological adaptations to extrauterine stresses. However, the molecular basis of these adaptations remains unclear. In this study, we analyzed the transcriptomes of seven organs from five mammalian species and identified a developmental shift in gene expression during the perinatal stage. The genes with low-to-high and high-to-low expression during this stage were found to be involved in various physiological adaptations, such as lipid metabolism, circadian rhythm, immune response, cell cycle, and cell division. These genes also formed mutually inhibitory toggle switch pairs, highlighting the importance of gene regulatory networks in the prenatal-to-postnatal transition. We propose a toggle switch model to investigate the mechanisms underlying the developmental shift in gene expression and the physiological adaptations during this transition.