The regulatory network is complex with many incoherent feedbacks and indirect regulatory interactions.
In spite of much detailed data, an integrated understanding of the processes regulating folliculogenesis is still lacking, and given the many incoherent feedbacks, several experimental findings appear counterintuitive.
In turn, their incoherent feedforward and negative feedback coupling mediated by the Erk/Gsk3 module is critical for robust segregation and sequential progression between naive and primed states before irreversible exit from pluripotency.
The presentation of the OSN model now begins with the introduction of the integral feedback and incoherent feed-forward motifs.
We first describe common network motifs that underlie cellular adaptation and homeostasis; these motifs utilize negative feedback and incoherent feedforward loops.
Below we illustrate how two common network motifs negative feedback and incoherent feedforward produce adaptation and homeostasis, as well as response thresholds.
Among the motifs described for homeostasis, integral feedback and incoherent feedforward with matching feedforward and perturbation strengths produce perfect adaptation with clear-cut, mechanistically definable thresholds.
For example, in stress-response pathways, rapid, robust adaptation often arises by coupling negative feedback and incoherent feedforward loops (El-Samad et al. 2005; Zhang et al. 2009).
Some network motifs, including proportional feedback loops, incoherent feedforward loops, and ultrasensitive motifs, generate responses in which the subthreshold response monotonically increases but remains very close to the baseline of the control situation.
Third, cells might sense relative changes in Yan, and respond to a constant fold-change in Yan levels using integral negative feedback or incoherent feedforward loops (Cohen-Saidon et al., 2009; Goentoro and Kirschner, 2009; Goentoro et al., 2009; Wartlick et al., 2011).
