Positive and negative regulation of Easter, a member of the serine protease family that controls dorsal-ventral patterning in the Drosophila embryo

Abstract

The sequential activities of four members of the trypsin family of extracellular serine proteases are required for the production of the ventrally localized ligand that organizes the dorsal-ventral pattern of the Drosophila embryo. The last protease in this sequence is encoded by easter, which is a candidate to activate proteolytically the ligand encoded by spätzle. Here, we demonstrate biochemically that the zymogen form of Easter is processed in vivo by a proteolytic cleavage event that requires the three upstream proteases. Processed Easter is present in extremely low amounts in the early embryo because it is rapidly converted into a high molecular mass complex, which may contain a protease inhibitor. Easter zymogen activation is also controlled by a negative feedback loop from Dorsal, the transcription factor at the end of the signaling pathway. Each of these regulated biochemical processes is likely to be important in generating the ventral-to-dorsal gradient of Dorsal protein that organizes cell fates in the early embryo.