Nudel, an unusual mosaic protease involved in defining the embryonic dorsal-ventral axis of Drosophila melanogaster
This is an Open Access Thesis
Dorsal-ventral polarity of the Drosophila embryo is determined by positional information that originates outside of the embryo. This information, which is created during oogenesis by the somatic follicle cells swrounding the oocyte, is utilized following fertilization to trigger a spatially regulated serine protease cascade in the extraembryonic perivitelline space. This protease cascade, which appears to be activated only on the presumptive ventral side of the embryo, generates the ligand for the Toll transmembrane protein that polarizes the embryo by inducing ventral development.This thesis presents evidence that nudel, a gene maternally required in somatic tissue for the formation of Toll's ligand, plays a key role in the transmission of the positional information that determines embryonic dorsal-ventral polarity. The nudel gene was cloned and found to be expressed in follicle cells when they are secreting egg shell components during oogenesis. However, nudel function can be disrupted after fertilization, hours to days after follicle cells have degenerated, suggesting that the nudel gene product persists in the fertilized egg to play a direct role in producing Toll's ligand during embryogenesis. The nudel gene encodes a large modular protein that structurally resembles extracellular matrix proteins. Consistent with its being an extracellular matrix component, nudel is required for structural integrity of the egg. Moreover, the nudel protein contains several motifs that may bind serine proteases or their zymogens, as well as two regions that resemble a serine protease catalytic domain. Strikingly, catalytic activity of the serine protease domain which lies at the center of nudel's primary structure appears to be required specifically for generating embryonic polarity. Based on these findings, it is proposed that nudel functions both to anchor and to trigger the protease cascade leading to Toll's ligand, and is therefore an essential component of the extracellular cue that defines embryonic dorsal-ventral polarity.