Shaping BMP Morphogen Gradients through Enzyme-Substrate Interactions

Carolyn E. Peluso, David Umulis, Young Jun Kim, Michael B. O'Connor, Mihaela Serpe

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Bone morphogenetic proteins (BMPs) regulate dorsal/ventral (D/V) patterning across the animal kingdom; however, the biochemical properties of certain pathway components can vary according to species-specific developmental requirements. For example, Tolloid (Tld)-like metalloproteases cleave vertebrate BMP-binding proteins called Chordins constitutively, while the Drosophila Chordin ortholog, Short gastrulation (Sog), is only cleaved efficiently when bound to BMPs. We identified Sog characteristics responsible for making its cleavage dependent on BMP binding. "Chordin-like" variants that are processed independently of BMPs changed the steep BMP gradient found in Drosophila embryos to a shallower profile, analogous to that observed in some vertebrate embryos. This change ultimately affected cell fate allocation and tissue size and resulted in increased variability of patterning. Thus, the acquisition of BMP-dependent Sog processing during evolution appears to facilitate long-range ligand diffusion and formation of a robust morphogen gradient, enabling the bistable BMP signaling outputs required for early Drosophila patterning. PaperFlick:

Original languageEnglish (US)
Pages (from-to)375-383
Number of pages9
JournalDevelopmental Cell
Volume21
Issue number2
DOIs
StatePublished - Aug 16 2011

Bibliographical note

Funding Information:
We thank Osamu Shimmi for communicating unpublished information and Stuart Newfeld for comments on the manuscript. We thank Chi-Hon Lee and Alan Hinnebusch for helpful discussions and suggestions. We are grateful to MaryJane Shimell for help in constructing the sog-HA transgene and to Seth Blair for Sog antibodies. We thank Peter Nguyen, Gabriel Peal, Jeremy Swan, and David Zhitomirsky for technical assistance. This work was supported in part by the Intramural Research Program at NIH. D.U. is supported by a grant from the Showalter Trust. M.B.O. is an Investigator with the Howard Hughes Medical Institute.

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