Graded Egfr activity patterns theDrosophilaeggshell independently of autocrine feedback

Abstract

The pattern of the Drosophila eggshell is determined by the establishment of a complex and stereotyped pattern of cell fates in the follicular epithelium of the ovary. Localized activation of the Epidermal growth factor receptor (Egfr) is essential for this patterning. Modulation of Egfr pathway activity in time and space determines distinct fates at their appropriate locations, but the details of how Egfr signaling is regulated and how the profile of Egfr activity corresponds to cell fate remain unclear. Here we analyze the effect of loss of various Egfr regulators and targets on follicle cell patterning, using a marker for follicle cell fate, and on the mature eggshell phenotype, using a novel eggshell marker. We show, contrary to current patterning models, that feedback regulation of Egfr activity by the autocrine ligand Spitz and the inhibitor Argos is not necessary for patterning. Given the cell-autonomous nature of the mutant phenotypes we observed, we propose instead that the pattern of cell fates is generated by spatial information derived directly from the germline ligand Gurken, without a requirement for subsequent patterning by diffusible Egfr regulators in the follicular epithelium.

Following the ‘tracks’: Tramtrack69 regulates epithelial tube expansion in the Drosophila ovary through Paxillin, Dynamin, and the homeobox protein Mirror

“…DA defects following mirr -RNAi resembled phenotypes produced by mirr [null] clones (Jordan et al, 2000; Zhao et al, 2000; Lachance et al, 2009; Fuchs et al, 2012), yet other features of these eggs differed significantly. mirr -RNAi eggs lacked DAs, yet DV polarity was unaffected: the dorsal surface of the egg was flat and the ventral surface was curved (Fig.…”

“…Expression of mirr at S10 in a dorsal anterior FC ‘saddle’ helps define the DV axis of the eggshell and embryo and determines the placement of the DAs (Nakamura et al, 2007; Lachance et al, 2009; Fuchs et al, 2012). We confirmed this reported S10 mirr mRNA expression (Figs.…”

“…mirr -RNAi eggs lacked DAs, yet DV polarity was unaffected: the dorsal surface of the egg was flat and the ventral surface was curved (Fig. 5G –G″; Lachance et al, 2009), and the embryos developing within these eggshells exhibited the normal pattern of ventral denticle belts (Fig. 5G–G″, arrowheads).…”

GIV/Girdin is a rheostat that fine-tunes growth factor signals during tumor progression

“…The second layer of complexity stems from the fact that switch-like 'on-and-off ' signaling undergoes further refinement into 'graded'-signaling in a timed manner. [88][89][90][91][92][93][94][95] Existence of molecules within the signal transduction cascade that introduce finetuned grades to receptor-initiated signals has only recently been described in yeast, the MAPK/ERK modulator, Ste5, [96][97][98][99][100] from whence the concept of "molecular rheostats" has emerged. Ste5 can grade MAPK signaling from low to high levels, much like variable resistors regulate current flowing within an electronic circuit do to the intensity of a light bulb.…”

Unit Operations of Tissue Development: Epithelial Folding

“…The origins of the other three primitives, in the forms of a midline triangle (M), two dorsolateral patches (R), and two L-shaped stripes (F), are less understood. The working hypothesis is that their formation depends on feedback modulation of signals provided by GRK and DPP (65, 67–69). Importantly, the midline shape describes cells that contribute to the future operculum, whereas the roof and floor primitives describe the spatial arrangement of cells that contribute to the upper and lower parts of the tubes in the future dorsal appendages (58, 59).…”