Affiliation:
1. The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
2. Imperial College, Department of Mathematics, London, UK.
Abstract
Morphogen gradients provide positional information during development.
To uncover the minimal requirements for morphogen gradient formation, we
have engineered a synthetic morphogen in
Drosophila wing primordia. We show that an
inert protein, green fluorescent protein (GFP), can form a detectable
diffusion-based gradient in the presence of surface-associated anti-GFP
nanobodies, which modulate the gradient by trapping the ligand and limiting
leakage from the tissue. We next fused anti-GFP nanobodies to the receptors
of Dpp, a natural morphogen, to render them responsive to extracellular GFP.
In the presence of these engineered receptors, GFP could replace Dpp to
organize patterning and growth in vivo. Concomitant expression of
glycosylphosphatidylinositol (GPI)–anchored nonsignaling receptors further
improved patterning, to near–wild-type quality. Theoretical arguments
suggest that GPI anchorage could be important for these receptors to expand
the gradient length scale while at the same time reducing leakage.
Funder
Wellcome
The Francis
Crick Institute
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
62 articles.
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