Response to the Dorsal Anterior Gradient of EGFR Signaling in Drosophila Oogenesis Is Prepatterned by Earlier Posterior EGFR Activation

Abstract

Spatially restricted epidermal growth factor receptor (EGFR) activity plays a central role in patterning the follicular epithelium of the Drosophila ovary. In midoogenesis, localized EGFR activation is achieved by the graded dorsal anterior localization of its ligand, Gurken. Graded EGFR activity determines multiple dorsal anterior fates along the dorsal-ventral axis but cannot explain the sharp posterior limit of this domain. Here, we show that posterior follicle cells express the T-box transcription factors Midline and H15, which render cells unable to adopt a dorsal anterior fate in response to EGFR activation. The posterior expression of Midline and H15 is itself induced in early oogenesis by posteriorly localized EGFR signaling, defining a feedback loop in which early induction of Mid and H15 confers a molecular memory that fundamentally alters the outcome of later EGFR signaling. Spatial regulation of the EGFR pathway thus occurs both through localization of the ligand and through localized regulation of the cellular response.

A Discrete Model of Drosophila Eggshell Patterning Reveals Cell-Autonomous and Juxtacrine Effects

“…However, work by Yakoby et al [34] contradicts this role of BMP signaling, and the most recent models [18] endorse the view that the posterior border of the competence region is set solely by early posterior Grk signaling. This hypothesis is strongly supported by recent experimental data [24]. This leaves unexplained the evidence for BMP pathway involvement in defining the anterior competence region, as well as the conflicting experimental results on this matter.…”

“…With regard to the controversy surrounding the influence of BMP pathway activity on DA formation, we suggest that the conflicting data can be reconciled by postulating an early BMP pathway signal that acts synergistically with the EGF-controlled mechanism identified by Fregoso Lomas et al [24]. These pathways may cooperate in early stages to define the anterior DA competence region.…”

Phenotypic rescue of aDrosophilamodel of mitochondrial ANT1 disease

“…The somatic cells of the ovary, in particular the follicle cells, play key roles in the patterning of the developing oocyte (Deng and Bownes, 1998; Poulton and Deng, 2007), and many molecular signaling pathways are involved (Roth et al, 1995; Neuman-Silberberg and Schüpbach, 1996; Rørth et al, 2000; Yamamoto et al, 2007; Stein et al, 2013; Fregoso Lomas et al, 2013), some of which are functionally conserved in vertebrates (Charlier et al, 2012). Moreover, cell proliferation and migration – crucial to the developmental function of the follicular epithelium – are commonly regulated by metabolite or redox signaling (Veal and Day, 2011; Hurd et al, 2012).…”

Epithelial Patterning, Morphogenesis, and Evolution: Drosophila Eggshell as a Model

“…Low levels of Gurken (Grk), a TGFα-like ligand, are synthesized near the oocyte nucleus and secreted by adjacent regions of the oocyte cortex; therefore, the Grk/Epidermal Growth Factor Receptor (EGFR) signaling in these stages is found in a posterior-to-anterior gradient (Figure 2A). One function of this early phase of Grk signaling is to prepattern the follicular epithelium, making the posterior part of the epithelium incapable of assuming an appendage-producing fate in response to a later inductive signal (Fregoso Lomas et al, 2013). This posterior repression of the appendage cell fate is mediated by T-box transcription factors Midline (Mid) and H15, which are induced by the early phase of Grk signaling and which repress Br (Fregoso Lomas et al, 2013).…”

“…One function of this early phase of Grk signaling is to prepattern the follicular epithelium, making the posterior part of the epithelium incapable of assuming an appendage-producing fate in response to a later inductive signal (Fregoso Lomas et al, 2013). This posterior repression of the appendage cell fate is mediated by T-box transcription factors Midline (Mid) and H15, which are induced by the early phase of Grk signaling and which repress Br (Fregoso Lomas et al, 2013). …”