Creating gradients by morphogen shuttling

Ben Zion Shilo*, Michal Haskel-Ittah, Danny Ben-Zvi, Eyal D. Schejter, Naama Barkai

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations


Morphogen gradients are used to pattern a field of cells according to variations in the concentration of a signaling molecule. Typically, the morphogen emanates from a confined group of cells. During early embryogenesis, however, the ability to define a restricted source for morphogen production is limited. Thus, various early patterning systems rely on a broadly expressed morphogen that generates an activation gradient within its expression domain. Computational and experimental work has shed light on how a sharp and robust gradient can be established under those situations, leading to a mechanism termed 'morphogen shuttling'. This mechanism relies on an extracellular shuttling molecule that forms an inert, highly diffusible complex with the morphogen. Morphogen release from the complex following cleavage of the shuttling molecule by an extracellular protease leads to the accumulation of free ligand at the center of its expression domain and a graded activation of the developmental pathway that decreases significantly even within the morphogen-expression domain.

Original languageAmerican English
Pages (from-to)339-347
Number of pages9
JournalTrends in Genetics
Issue number6
StatePublished - Jun 2013
Externally publishedYes

Bibliographical note

Funding Information:
We thank the reviewers for insightful comments that helped to shape this review. This work was supported by the European Research Council, Israel Science Foundation, Minerva, and the Helen and Martin Kimmel Award for Innovative Investigations to N.B., who is the incumbent of the Lorna Greenberg Scherzer Professorial Chair, and the Minerva Foundation to B-Z.S., who is an incumbent of the Hilda and Cecil Lewis Professorial Chair in Molecular Genetics.


  • BMP
  • Chordin
  • Embryonic patterning
  • Morphogen gradients
  • Shuttling
  • Spätzle
  • Toll


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