DPP Movie


In the early Drosophila embryo, decapentaplegic, or DPP, a BMP-type ligand, is key in assigning identity to all dorsal structures. DPP is transcribed uniformly throughout the dorsal domain, yet it forms an activity gradient, such that there is a low level of signaling in the dorsal lateral regions, which will form the dorsal ectoderm, and a high level of signaling in the dorsal most cells, which will form the dorsal most tissue, the amnioserosa. Formation of this activity gradient requires several secreted modulators. The expression domain of Dpp is flanked laterally by the region where short gastrulation, or Sog, a Dpp-binding protein, is produced.

The following events occur in the area between the embryo and the perivitelline membrane known as the perivitelline space. Sog makes a complex with Dpp that inhibits the Dpp signal from spreading into the lateral regions. At the same time, this complex, which also contains twisted gastrulation, or Tsg, protects Dpp from degradation and receptor mediated internalization, and also allows it to diffuse. As the complexes move towards the dorsal midline, they encounter a protease, Tld, which cleaves Sog when it is bound to its co-substrate, Dpp. This results in the destruction of the complex and the release of Dpp.

Released Dpp has two possible fates: it can bind to a receptor and signal, or it can be recaptured by another Sog/Tsg complex. When Sog levels are high, as in the lateral domain, the probability of recapture is high, while at the dorsal midline, Dpp is more likely to bind to receptor and signal. Reiterated cycles of complex formation, diffusion, and destruction by Tld generate a net movement of the Dpp from the lateral domain towards the midline.

It has been shown that the favored species for the Sog-mediated facilitated diffusion is a BMP heterodimer, that is Dpp and another Bmp-type ligand screw. Sog has both positive and negative effects on the signaling of Dpp. It inhibits signaling locally, while it also facilitates the redistribution of the ligands to the region where a high level of signaling is required. Thus, without Sog, there is no amnioserosa, the tissue that is specified at peak levels of signaling.

The balance between the positive and negative activities of Sog is regulated by Tld, the protease which cleaves Sog only when it is bound to a co-substrate, such as Dpp.

In this study, we propose that the co-substrate dependents of Sog degradation facilitates long range diffusion. When we replaced endogenous Sog with a Sog variant that could be cleaved by TLD independent of the cosubstrate, we found that Bmp-independent Sog was less sufficient as shuttling the Bmp ligands and therefore produced a shallower Bmp gradient profile.

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