Transcriptional interpretation of the EGF receptor signaling gradient

Abstract

Epidermal growth factor receptor (EGFR) controls a wide range of developmental events, from body axes specification in insects to cardiac development in humans. During Drosophila oogenesis, a gradient of EGFR activation patterns the follicular epithelium. Multiple transcriptional targets of EGFR in this tissue have been identified, but their regulatory elements are essentially unknown. We report the regulatory elements of broad ( br ) and pipe ( pip ), two important targets of EGFR signaling in Drosophila oogenesis. br is expressed in a complex pattern that prefigures the formation of respiratory eggshell appendages. We found that this pattern is generated by dynamic activities of two regulatory elements, which display different responses to Pointed, Capicua, and Mirror, transcription factors involved in the EGFR-mediated gene expression. One of these elements is active in a pattern similar to pip , a gene repressed by EGFR and essential for establishing the dorsoventral polarity of the embryo. We demonstrate that this similarity of expression depends on a common sequence motif that binds Mirror in vitro and is essential for transcriptional repression in vivo.

Mirror repressespipeexpression in follicle cells to initiate dorsoventral axis formation inDrosophila

“…Two related papers on pipe regulation have appeared while this article was in revision (Technau et al, 2011;Fuchs et al, 2012). (Astigarraga et al, 2007;Cinnamon et al, 2008).…”

EGFR-dependent network interactions that pattern Drosophila eggshell appendages

“…The threshold of repression of G 3 by G 1 (br repression by Pnt) is set to a low value, 31 0.1, ensuring that br is repressed without a considerable delay following the induction of its repressor ( Yakoby et al, 2008b;Boisclair Lachance et al, 2009;Fuchs et al, 2011). Similarly, the activation thresholds of G 5 by G 4 , and G 2 by G 5 are chosen to be low: 54  25 0.1.…”

“…Description of the fluorescence in situ hybridization protocol and dpERK staining are provided elsewhere (Fuchs et al, 2011;Zartman et al, 2009). Digoxigenin-and biotin-labeled antisense probes were transcribed in vitro, and purified with RNeasy mini kit (Qiagen).…”

Gene regulation during Drosophila eggshell patterning

“…2C and 3A). The identification of these enhancers made it possible to determine whether the effects of the key transcription factors controlling br are direct and whether they affect the early or the late phases of br expression (29). For instance, it was established that MIRR controls both enhancers, but with opposite signs: repressing brE and activating brL (Fig.…”

“…Specifically, dissection of the genomic region of br revealed the existence of two distinct enhancers, early and late, that combine their activities over time to generate the dynamic expression of br in the follicle cells ( Fig. 3A) (29). An early enhancer (brE) drives uniform expression before stage 10 of oogenesis.…”