Fig. 8. (A) Ras is required for pipe repression and dorsal appendage morphogenesis. Higher levels of Ras protein are required for the dorsoventral patterning of the eggshell (black arrow) than for embryonic dorsoventral patterning, which begins with the cell-autonomous repression of pipe by Ras signaling (gray 
line) in dorsal and lateral follicle cells. This eggshell vs. embryo difference in requirement for Ras may be due to an eggshell-specific requirement for higher levels of Ras during Egfr signal amplification. Ras is required for dorsal follicle cell morphogenesis either through transcriptional activation of morphogenesis genes (solid black arrow) or through the direct cytoplasmic activation of cytoskeletal or adhesion molecules (dashed black arrow). One outcome of Ras signaling is the basal localization of E-Cad in dorsal midline cells. (B) A hypothesis for embryonic dorsoventral patterning: dorsal Egfr signaling restricts pipe mRNA (purple) to the ventral-most 40% of follicle cells. Pipe-positive cells activate a serine protease cascade in the perivitelline space separating the vitelline membrane (orange) and the oocyte. This cascade culminates in cleavage of the Spz zymogen to produce the ventral determinant C-Spz (green asterisks), the activity of which is negated by N-Spz and/or other inhibitors (red lines). This inhibition process normally reduces the ventral-determining region to 20% of the embryonic circumference, and, in embryos from Ras mosaic egg chambers, can completely overcome isolated regions of ectopic ventral activity caused by a Ras clone. This ‘ventral-most’ 20% region then instructs the nuclear Dorsal gradient along the dorsoventral axis (blue nuclei), and highest levels of nuclear Dorsal result in Twist protein expression (red nuclei).
