Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient.
Nat Commun
; 14(1): 758, 2023 02 10.
Article
em En
| MEDLINE
| ID: mdl-36765094
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 gradient hypomorphs in vivo. The speed and propensity of direct Hh switching between HS therefore shapes the Hh gradient, revealing a scalable design principle in morphogen-patterned tissues.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Drosophila
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article