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You are here: Home / Teams / Epithelial differentiation and morphogenesis in Drosophila - M. Grammont / Publications / Absolute requirement of cholesterol binding for Hedgehog gradient formation in Drosophila.

Absolute requirement of cholesterol binding for Hedgehog gradient formation in Drosophila.

Antoine Ducuing, Bertrand Mollereau, Jeffrey D Axelrod, and Stephane Vincent (2013)

Biol Open, 2(6):596-604.

How morphogen gradients are shaped is a major question in developmental biology,but remains poorly understood. Hedgehog (Hh) is a locally secreted ligand that reaches cells at a distance and acts as a morphogen to pattern the Drosophila wing and the vertebrate neural tube. The proper patterning of both structures relies on the precise control over the slope of Hh activity gradient. A number of hypotheses have been proposed to explain Hh movement and hence graded activity of Hh. A crux to all these models is that the covalent binding of cholesterol to HhN-terminus is essential to achieve the correct slope of the activity gradient. Still, the behavior of cholesterol-free Hh (Hh-N) remains controversial: cholesterol has been shown to either increase or restrict Hh range depending on the experimental setting. Here, in fly embryos and wing imaginal discs, we show that cholesterol-free Hh diffuses at a long-range. This unrestricted diffusion of cholesterol-free Hh leads to an absence of gradient while Hh signaling strength remains uncompromised. These data support a model where cholesterol addition restricts Hh diffusion and can transform a leveled signaling activity into a gradient. In addition, our data indicate that the receptor Patched is not able to sequester cholesterol-free Hh. We propose that a morphogen gradient does not necessarily stem from the active transfer of a poorly diffusing molecule, but can be achieved by the restriction of a highly diffusible ligand.

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