Editors' ChoiceDevelopment

Cells Remember Dpp and Show Enhanced Responsiveness

Science's STKE  15 Mar 2005:
Vol. 2005, Issue 275, pp. tw96
DOI: 10.1126/stke.2752005tw96

Decapentaplegic (Dpp) is a bone morphogenetic protein (BMP) family member that is involved in specification of the dorsal-ventral axis. In Drosophila, dpp is expressed in a broad area of the dorsal part of the embryo, and a gradient is subsequently established through interaction with Sog (short gastrulation), which inhibits Dpp's interaction with its receptor and Tsg (twisted gastrulation). Cleavage of Sog by the metalloprotease Tld (tolloid) releases Dpp, allowing it to interact with its receptor. Wang and Ferguson created an immunostaining method that selectively detects receptor-bound Dpp, thus identifying the Dpp-responsive region without visualizing the Dpp-secreting cells. In sog mutants, receptor-bound Dpp was restricted to an area near the Dpp-producing cells, indicating that Sog is necessary for long-range movement of Dpp by preventing binding to the receptor in cells adjacent to the site of production. In contrast, tsg mutants showed reduced Dpp receptor binding, which suggests that Tsg promotes or assists in Dpp-receptor interactions. Screw (Scw), another BMP family member that binds a different receptor, synergizes with Dpp, and receptor-bound Scw was also observed in the same dorsally restricted pattern as was Dpp. In the absence of Scw, receptor-bound Dpp was diminished. In contrast to Dpp, in sog mutants, Scw was capable of long-range transport, and Dpp-expressing cells distal from the site of Scw production were responsive to Scw. Injection of an mRNA for a constitutively active form of the Dpp receptor (Tkv-a), but not mRNA for the wild-type receptor, promoted ectopic recruitment of Dpp to the cells near the injection site and suppressed Dpp binding and signaling in adjacent, noninjected cells. This may reflect a positive feedback mechanism whereby previous Dpp signaling (through the constitutively active receptor in this case) enhances future responsiveness to Dpp. In mutant embryos that could not effectively stimulate gene expression in response to Dpp, the ability to limit Dpp receptor binding and responsiveness to the appropriate area was also impaired. Thus, the positive feedback mechanism that contributes to restricting Dpp responsiveness involves the transcriptional regulatory functions of Dpp signaling.

Y.-C. Wang, E. L. Ferguson, Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning. Nature 434, 229-234 (2005). [PubMed]