During early Drosophila embryogenesis, several zygotic gene products act to establish a posttranscriptional activity gradient of the morphogen DPP. Among these molecules, Tolloid, a putative metalloprotease related to BMP-1, enhances DPP function, while SOG, an ortholog of the Xenopus organizer Chordin, inhibits DPP function. Using epistasis tests and a Xenopus secondary axis induction assay, we show that TLD negates the inhibitory effects of SOG/CHD on DPP/BMP-type ligands. In transient transfection assays, we demonstrate that TLD cleaves SOG and that cleavage is stimulated by DPP. We propose that formation of the embryonic DPP activity gradient involves the opposing effects of SOG inhibiting DPP and TLD processing SOG to release DPP from the inhibitory complex.
Bibliographical noteFunding Information:
We thank Drs. E. De Robertis, R. Harlad, and N. Ueno for the CHD, noggin, and dominant-negative BMP receptor cDNAs, and S. Piccolo, E. De Robertis, and Ethan Bier for communication of results prior to publication. We are grateful to Bettina Seri for technical support. We thank Lucy Cherbas for advice regarding culturing of S2 cells. We also thank Thao Nguyen for construction of epitope-tagged TLD and Mike Hoffman for UAS-TLD transformant lines. We are grateful to the Genetics Institute for supplying purified BMP-2 and BMP-4 proteins, and to Wylie Vale for the gift of activin. This manuscript was improved by the thoughtful comments of Larry Marsh and Kavita Arora. The authors gratefully acknowledge K. Matthews and the resources of the National Drosophila Stock Center in Bloomington, IN. This work was supported by a MEC/Fulbright and NATO fellowships to G. M. and National Institutes of Health grants GM54704 and HD01158 to K. C. and GM00599 and GM47462 to M. B. O.
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