Exosome secretion is required for Sonic Hedgehog dispersal and signal gradient formation in the embryonic limb bud mesenchyme.

Exosome secretion is required for Sonic Hedgehog (Shh) dispersal and short-range Shh signaling gradient formation in embryonic limb bud mesenchyme, both in vitro and in vivo.

• Why it matters: Carrier-assisted diffusion and cytoneme transport are known for Hedgehog spread, but how these mechanisms specifically pattern mesenchymal tissues is unclear.
• What they did: Using signaling assays with quantitative microscopy and a synchronous release system, the study tracked Shh trafficking and showed it passes through the exosome biogenesis pathway in limb bud mesenchymal cells.
• The result: Shh-bound exosomes diffuse extracellularly and also move along cytonemes; exosome secretion is essential for short-range Shh gradients in vitro and contributes to shaping Shh protein gradients in the limb bud in vivo.

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