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Hedgehog (Hh)

Hedgehog (Hh) signalling was initially characterised through its role in patterning the Drosophila larval epidermis, where spatially restricted expression of Hh – the single Hh family protein present in flies – maintains expression of the Drosophila Wnt1 orthologue wingless (wg) in neighbouring cells. In vertebrates, the spatially restricted expression of sonic hedgehog (Shh) – the most extensively studied of the vertebrate Hh proteins – in the developing limb bud plays a remarkably similar role, regulating cell proliferation and patterning of the appendages. Shh functions as an axon guidance cue and plays a crucial role in tissue homeostasis as well as in the regenerative response to injury in a number of organs, including the bladder, airway, heart and fin. Vertebrates have two Patched genes (Ptch1 and Ptch2), the products of which play partially redundant roles in Hh reception. Hh proteins are found in many animals, from jellyfish to human. Hh proteins bind to several other type 1 membrane proteins that are required for pathway activation: vertebrate Cdo and Boc and their Drosophila counterparts Ihog and Boi, and the vertebrate-specific Gas1. These co-receptors act semi-redundantly to mediate Hh pathway activation. The expression of Ptc/Ptch and Hhip1 is induced upon Hh pathway activation, creating a negative-feedback loop.

References

1.Lee RT,et al. Development. 2016 Feb 1;143(3):367-72.

GPCR/G Protein

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