The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through Notch activation

Abstract

Recent studies in vertebrates and Drosophila melanogaster have revealed that Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis. In these processes, a homeobox-containing transcription factor is responsible for spatially regulating fringe (fng) expression and thus directing activation of the Notch pathway along the fng expression border. Here we show that this may be a general mechanism for patterning epithelial cell layers. At three stages in Drosophila oogenesis, mirror (mirr) and fng have complementary expression patterns in the follicle-cell epithelial layer, and at all three stages loss of mirr enlarges, and ectopic expression of mirr restricts, fng expression, with consequences for follicle-cell patterning. These morphological changes are similar to those caused by Notch mutations. Ectopic expression of mirr in the posterior follicle cells induces a stripe of rhomboid (rho) expression and represses pipe (pip), a gene with a role in the establishment of the dorsal-ventral axis, at a distance. Ectopic Notch activation has a similar long-range effect on pip. Our results suggest that Mirror and Notch induce secretion of diffusible morphogens and we have identified TGF-beta (encoded by dpp) as such a molecule in germarium. We also found that mirr expression in dorsal follicle cells is induced by the EGF-receptor (EGFR) pathway and that mirr then represses pip expression in all but the ventral follicle cells, connecting EGFR activation in the dorsal follicle cells to repression of pip in the dorsal and lateral follicle cells. Our results suggest that the differentiation of ventral follicle cells is not a direct consequence of germline signalling, but depends on long-range signals from dorsal follicle cells, and provide a link between early and late events in Drosophila embryonic dorsal-ventral axis formation.

Fringe‐dependent notch activation and tramtrack function are required for specification of the polar cells in Drosophila oogenesis

“…The expression of Fringe is also observed after the germarium stage in the prepolar cells ( Fig. 1F,G ;Jordan et al, 2000;Zhao et al, 2000).…”

“…Mirror represses fringe in the germarium generating a fringe expression border. As seen in other tissues, this border may provide specificity for Notch activation (Jordan et al, 2000;Grammont and Irvine, 2001;Fig. 1A1).…”

“…1A2, 3;McGregor et al, 2002;Torres et al, 2003). The dpp pathway may also be involved in specification of the stalk and polar cell precursors in the germarium (Jordan et al, 2000). Delta follicle cell clones also result in a loss of stalk cells, indicating that the Notch pathway is active in this third step as well (Ruohola et al, 1991;Lopez-Schier and St. Johnston, 2001).…”

“…In the wing disc, Fringe inhibits Notch activation by Serrate, but enhances Notch activation by Delta (Doherty et al, 1996;Panin et al, 1997). In the wing, eye, and ovary, a homeobox transcription factor has been shown to regulate fringe expression, resulting in activation of Notch at the fringe expression border (Domingues and de Celis, 1998;Rauskolb et al, 1999;Jordan et al, 2000;Zhao et al, 2000). In addition, Notch activity is modulated by the cytoplasmic protein Numb, most likely in a mechanism that involves endocytosis.…”

“…This positional effect is in accordance with the restriction of fringe expression to the prepolar cells at this stage. Finally, although the homeobox transcription factor Mirror is required to define fng expression in the germarium and, thus, is involved in the encapsulation of individual egg chambers (Jordan et al, 2000), mirror is not required in this later step of polar cell differentiation, suggesting that the pattern of fringe expression is generated through other means.…”