Abstract
Patterning the dorsal surface of the Drosophila blastoderm embryo requires Decapentaplegic (Dpp) and Screw (Scw), two BMP family members. Signaling by these ligands is regulated at the extracellular level by the BMP binding proteins Sog and Tsg. We demonstrate that Tsg and Sog play essential roles in transporting Dpp to the dorsal-most cells. Furthermore, we provide biochemical and genetic evidence that a heterodimer of Dpp and Scw, but not the Dpp homodimer, is the primary transported ligand and that the heterodimer signals synergistically through the two type I BMP receptors Tkv and Sax. We propose that the use of broadly distributed Dpp homodimers and spatially restricted Dpp/Scw heterodimers produces the biphasic signal that is responsible for specifying the two dorsal tissue types. Finally, we demonstrate mathematically that heterodimer levels can be less sensitive to changes in gene dosage than homodimers, thereby providing further selective advantage for using heterodimers as morphogens.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 873-886 |
| Number of pages | 14 |
| Journal | Cell |
| Volume | 120 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 25 2005 |
Bibliographical note
Funding Information:We thank MaryJane Shimell and David Zhitomirsky for help in producing the Dpp-HA and Scw-HA genomic transgenes. We thank Kavita Arora for the gift of Scw antibody. The manuscript was improved by the thoughtful editing of MaryJane Shimell and Guillermo Marques and several anonymous reviewers. We thank Yu Chiun Wang, Chip Ferguson, and Arthur Lander for communication of results prior to publication. This work was funded in part by PHS grant GM29123 (to H.O.). D.U. is supported by the NIH Biotechnology Training Grant. M.B.O. is an Investigator with the Howard Hughes Medical Institute.