title: Drosophila eggshell 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.
authors: Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ 08544, USA.
authors: Nir
authors: N
authors: Yakoby
authors: Jessica
authors: J
authors: Lembong
authors: Trudi
authors: T
authors: Schüpbach
authors: Stanislav Y
authors: SY
authors: Shvartsman
mesh_terms: D000818:Animals; D019521:Body Patterning; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology*; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D010063:Ovum / Q000166:cytology / Q000254:growth & development*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D012097:Repressor Proteins; D066246:ErbB Receptors