Signal Transduction Pathways in Development: Hedgehog Proteins and their Receptors


The Hedgehog proteins comprise a family of secreted signalling proteins of crucial importance for development of metazoan animals. The signalling pathway downstream of Hedgehog proteins is highly conserved in evolution. Loss or misactivation of the Hh signalling pathway can lead to pathogenesis.

Keywords: hedgehog; development; signal transduction

Figure 1.

Localization of proteins and transcripts in embryos. (a) Drosophila melanogaster embryo immunostained for (Hh) protein. (b) D. melanogaster embryo immunostained for Engrailed protein. (c) Gallus gallus embryo hybridized with a probe for the shh gene. Arrows indicate shh expression in forelimbs (wingbuds). (d) Detail of embryo shown in (c). The letters f and n indicate floorplate and notochord respectively.

Figure 2.

Localization of proteins in wing imaginal disc of Drosophila melanogaster. Indicated are the different antigens that were detected. In green, Patched (Ptc) protein; in red, Cubitus interruptus (Ci) protein; and in blue, Hedgehog (Hh) protein. The bottom right panel shows all of the colours combined. The arrow indicates the low levels of Ci protein seen at the interface with the Hh expressing cells.

Figure 3.

Schematic representation of the Hedgehog (Hh) signalling pathway. On the left the pathway is shown as it is thought to proceed in the absence of Hh protein and, on the right, in the presence of Hh. The slimb and PKA genes are not included in this figure. (a) The Ptc protein on the plasma membrane is active (dark blue) in the absence of the Hh protein, thus keeping the Smo protein in an inactive state (light blue). A complex containing Cos, Ci, Fu and Su(fu) proteins is bound to microtubules. A smaller, repressor form of Ci is released from this complex through cleavage of the full‐length protein. This form of Ci represses transcription of target genes in the nucleus (for instance, the hedgehog (hh) gene itself). (b) Hh protein secreted from producing cells, with the help of Disp, can be bound to Ttv on receiving cells. When bound to Ptc it inactivates this protein. This releases Smo from inhibition by Ptc (Ptc is now inactive (light blue), while Smo is active (dark blue)). The Cos‐containing complex falls apart and releases full‐length Ci protein. At the same time, Fu is phosphorylated. In the nucleus, full‐length Ci protein activates transcription of target genes (for instance patched (ptc), decapentaplegic (dpp) and wingless (wg)). Abbreviations: Smo, Smoothened; Ptc, Patched; Hh, Hedgehog; Ttv, Tout velu; Disp, Dispatched; Cos, Costal 2; Fu, Fused; Su(fu), Suppressor of fused; Ci, Cubitus interruptus.



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Further Reading

Goodrich L and Scott MP (1998) Hedgehog and patched in neural development and disease. Neuron 21: 1243–1257.

Goodrich LV, Johnson RL, Milenkovic L, McMahon JA and Scott MP (1996) Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes and Development 10: 301–312.

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Shimeld SM (1999) The evolution of the hedgehog gene family in chordates: insights from amphioxus hedgehog. Development Genes and Evolution 209: 40–47.

Shubin N, Tabin C and Carroll S (1997) Fossils, genes and the evolution of animal limbs. Nature 388: 639–648.

van den Heuvel M and Ingham PW (1996) ‘Smoothening’ the path for hedgehogs. Trends in Cell Biology 66: 451–453.

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How to Cite close
van den Heuvel, Marcel(Apr 2001) Signal Transduction Pathways in Development: Hedgehog Proteins and their Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0002329]