Drosophilaeggshell is patterned by sequential action of feedforward and feedback loops

Abstract

During Drosophila oogenesis, patterning activities of the EGFR and Dpp pathways specify several subpopulations of the follicle cells that give rise to dorsal eggshell structures. The roof of dorsal eggshell appendages is formed by the follicle cells that express Broad (Br), a zinc-finger transcription factor regulated by both pathways. EGFR induces Br in the dorsal follicle cells. This inductive signal is overridden in the dorsal midline cells, which are exposed to high levels of EGFR activation, and in the anterior cells, by Dpp signaling. We show that the resulting changes in the Br pattern affect the expression of Dpp receptor thickveins (tkv), which is essential for Dpp signaling. By controlling tkv, Br controls Dpp signaling in late stages of oogenesis and, as a result, regulates its own repression in a negative-feedback loop. We synthesize these observations into a model, whereby the dynamics of Br expression are driven by the sequential action of feedforward and feedback loops. The feedforward loop controls the spatial pattern of Br expression, while the feedback loop modulates this pattern in time. This mechanism demonstrates how complex patterns of gene expression can emerge from simple inputs, through the interaction of regulatory network motifs.

Position matters: Variability in the spatial pattern of BMP modulators generates functional diversity

“…However, the effect of posterior mad-clones on the expression of the effector Broad-Complex (Peri and Roth, 2000) is evidence that in dorsal regions of the egg chamber Dpp spreads more posteriorly. Furthermore, a transition in pMad staining from a purely AP to a DV pattern has been reported during stage 10A-B of oogenesis (Yakoby et al, 2008b). These data suggest that in the mid-stage egg chamber a stripe of dpp expressing cells is transformed into a diagonal gradient of Dpp that spreads posteriorly in dorsal regions but is restricted anteriorly in ventral regions.…”

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

“…Primary antibodies used for staining were rabbit anti-pMad (diluted as 1:4000) [52], rat anti-DE-Cadherin (diluted 1:20, Developmental Studies Hybridoma Bank, DCAD2), mouse anti-Wg (diluted 1:50, Developmental Studies Hybridoma Bank, 4D4), rabbit anti-beta-GAL (diluted 1:8000, Cappel). Secondary antibodies, conjugated to Cy3, were used for detection (diluted 1:200, Jackson ImmunoResearch Lab).…”

Gene regulation during Drosophila eggshell patterning

“…Work over the past decade has identified the transcriptional factors that control these genes and has started to connect them in a regulatory network (2,(12)(13)(14)(15)(16)(17)(18). Based on this network, we can predict how the expression patterns of multiple genes will respond to a range of genetic perturbations, including the quantitative changes in the distribution and levels of inductive signals (Fig.…”

“…The dorsoventral gradient of EGFR signaling controls br through a feedforward loop, a network motif in which EGFR activates both br and its repressor (17,18,20,21). The induction threshold for the repressor is higher than that for br, which explains why it is expressed only in cells exposed to intermediate levels of GRK.…”

“…These effects are mediated by two distinct repression events, which are separated both in time and in space. The anterior repression depends on the anterior gradient of DPP signaling (2,17,23), which controls br through a two-tier cascade that involves repression of BRK, a direct target of DPP in multiple stages of Drosophila development (24)(25)(26). The posterior repression of br relies on the earlier phase of EGFR signaling, when the oocyte nucleus is located at the posterior of the oocyte.…”