Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient.

ABSTRACT: Cellular differentiation is directly determined by concentration gradients of morphogens. As a central model for gradient formation during development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in Drosophila wing and eye discs. What is not known is how extracellular Hh spread is achieved and how it translates into precise gradients. Here we show that two separate binding areas located on opposite sides of the Hh molecule can interact directly and simultaneously with two heparan sulfate (HS) chains to temporarily cross-link the chains. Mutated Hh lacking one fully functional binding site still binds HS but shows reduced HS cross-linking. This, in turn, impairs Hhs ability to switch between both chains in vitro and results in striking Hh gr

SUBMITTER: Gude F 

PROVIDER: S-EPMC9918555 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature